{"protocolSection":{"identificationModule":{"nctId":"NCT03864042","orgStudyIdInfo":{"id":"ARRAY-818-103"},"secondaryIdInfos":[{"id":"C4221003","type":"OTHER","domain":"Alias Study Number"},{"id":"2019-001036-66","type":"EUDRACT_NUMBER"},{"id":"2019","type":"NIH","link":"https://reporter.nih.gov/quickSearch/2019"}],"organization":{"fullName":"Pfizer","class":"INDUSTRY"},"briefTitle":"Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors","officialTitle":"An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors"},"statusModule":{"statusVerifiedDate":"2024-05","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2018-01-02","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2022-07-11","type":"ACTUAL"},"completionDateStruct":{"date":"2023-05-29","type":"ACTUAL"},"studyFirstSubmitDate":"2019-02-01","studyFirstSubmitQcDate":"2019-03-04","studyFirstPostDateStruct":{"date":"2019-03-06","type":"ACTUAL"},"resultsFirstSubmitDate":"2023-07-07","resultsFirstSubmitQcDate":"2024-05-17","resultsFirstPostDateStruct":{"date":"2024-09-27","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-05-17","lastUpdatePostDateStruct":{"date":"2024-09-27","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Pfizer","class":"INDUSTRY"},"collaborators":[{"name":"Pierre Fabre Laboratories","class":"INDUSTRY"}]},"oversightModule":{"oversightHasDmc":false,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false},"descriptionModule":{"briefSummary":"This is an open-label, 3-arm, fixed-sequence study to evaluate the effect of single and multiple oral doses of encorafenib in combination with binimetinib on the single oral dose pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme probe substrates using a probe cocktail, on an organic anion-transporting polypeptide/breast cancer resistance protein (OATP/BCRP) substrate using rosuvastatin and on a CYP2B6 substrate using bupropion. The effect of multiple oral doses of the moderate cytochrome P450 (CYP) inhibitor modafinil on encorafenib in combination with binimetinib will also be assessed. The study will have 2 treatment phases, a drug-drug interaction (DDI) phase followed by a post-DDI phase."},"conditionsModule":{"conditions":["Advanced Solid Tumors","Metastatic Melanoma"],"keywords":["solid tumor","melanoma"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE1"],"designInfo":{"allocation":"NON_RANDOMIZED","interventionModel":"SEQUENTIAL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"NONE"}},"enrollmentInfo":{"count":56,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Arm 1 - CYP Probe Cocktail","type":"EXPERIMENTAL","description":"Patients will receive a single oral dose of the CYP Probe Cocktail on Day -7, Day 1, and Day 14:\n\n* 25 mg losartan oral tablet\n* 30 mg dextromethorphan oral capsule\n* 50 mg caffeine oral liquid\n* 20 mg omeprazole oral capsule\n* 2 mg midazolam oral syrup\n\nencorafenib/binimetinib continuous daily dosing starting Day 1:\n\n* 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)\n* 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)\n\nAll drugs will be taken within 10 minutes.","interventionNames":["Drug: losartan","Drug: dextromethorphan","Drug: caffeine","Drug: omeprazole","Drug: midazolam","Drug: encorafenib","Drug: binimetinib"]},{"label":"Arm 2 - Rosuvastatin and Bupropion","type":"EXPERIMENTAL","description":"Patients will receive a single oral dose of rosuvastatin and bupropion once on Day -7, Day 1 and Day 14:\n\n* 10 mg rosuvastatin oral tablet\n* 75 mg bupropion immediate release (IR) oral tablet\n\nencorafenib/binimetinib continuous daily dosing starting Day 1:\n\n* 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)\n* 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)\n\nAll drugs will be taken within 10 minutes.","interventionNames":["Drug: rosuvastatin","Drug: bupropion immediate release (IR)","Drug: encorafenib","Drug: binimetinib"]},{"label":"Arm 3 - Modafinil","type":"EXPERIMENTAL","description":"Patients will begin encorafenib/binimetinib continuous daily dosing starting Day 1:\n\n* 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)\n* 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)\n\nthen receive continuous treatment of modafinil on Day 15 through Day 21:\n\n\\- 400 mg modafinil tablet once daily (QD)","interventionNames":["Drug: encorafenib","Drug: binimetinib","Drug: modafinil"]}],"interventions":[{"type":"DRUG","name":"losartan","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail"]},{"type":"DRUG","name":"dextromethorphan","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail"]},{"type":"DRUG","name":"caffeine","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail"]},{"type":"DRUG","name":"omeprazole","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail"]},{"type":"DRUG","name":"midazolam","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail"]},{"type":"DRUG","name":"rosuvastatin","description":"taken orally","armGroupLabels":["Arm 2 - Rosuvastatin and Bupropion"]},{"type":"DRUG","name":"bupropion immediate release (IR)","description":"taken orally","armGroupLabels":["Arm 2 - Rosuvastatin and Bupropion"]},{"type":"DRUG","name":"encorafenib","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail","Arm 2 - Rosuvastatin and Bupropion","Arm 3 - Modafinil"]},{"type":"DRUG","name":"binimetinib","description":"taken orally","armGroupLabels":["Arm 1 - CYP Probe Cocktail","Arm 2 - Rosuvastatin and Bupropion","Arm 3 - Modafinil"]},{"type":"DRUG","name":"modafinil","description":"taken orally","armGroupLabels":["Arm 3 - Modafinil"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Area Under the Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Plasma Midazolam on Day -7, Day 1, and Day 14","description":"AUClast is area under the concentration-time profile (AUC) from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Paraxanthine was the metabolite of caffeine.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Hydroxybupropion was the metabolite of bupropion.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14"},{"measure":"Ae0-8 of E-3174 on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. E-3174 was the metabolite of losartan.","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14"},{"measure":"Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14"},{"measure":"Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. Dextrorphan was the metabolite of dextromethorphan.","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14"},{"measure":"Cmax of Plasma Encorafenib on Day 14 and Day 21 in Arm 3","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Cmax of Plasma LHY746 on Day 14 and Day 21 in Arm 3","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"AUClast of Plasma Encorafenib on Day 14 and Day 21 in Arm 3","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"AUClast of Plasma LHY746 on Day 14 and Day 21 in Arm 3","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"}],"secondaryOutcomes":[{"measure":"Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight (MW), which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. 1-OH midazolam was the metabolite of midazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Ratio of AUC From Time Zero Extrapolated to Infinity (AUCinf) Values of the Metabolite Compared to Parent (MRAUCinf) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14","description":"MRAUCinf is the ratio of AUCinf values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUCinf (metabolite) × MW (parent)\\] / \\[AUCinf (parent) × MW (metabolite)\\]. 1-OH midazolam was the metabolite of midazolam. AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. Paraxanthine was the metabolite of caffeine.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRAUClast for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRAUCinf for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14","description":"MRAUCinf is the ratio of AUCinf values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUCinf (metabolite) × MW (parent)\\] / \\[AUCinf (parent) × MW (metabolite)\\]. 5-OH Omeprazole was the metabolite of omeprazole. AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRAUClast for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. Hydroxybupropion was the metabolite of bupropion.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRAUClast for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. 1-OH midazolam was the metabolite of midazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRCmax for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. Paraxanthine was the metabolite of caffeine.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRCmax for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRCmax for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. Hydroxybupropion was the metabolite of bupropion.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"MRCmax for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Ratio of Ae0-8 Values of the Metabolite Compared to Parent (MRAe0-8) for E-3174/Losartan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. MRAe0-8 is the ratio of Ae0-8 values of the metabolite compared to parent, corrected for molecular weight. E-3174 was the metabolite of losartan.","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14"},{"measure":"MRAe0-8 for Dextrorphan/Dextromethorphan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. MRAe0-8 is the ratio of Ae0-8 values of the metabolite compared to parent, corrected for molecular weight. Dextrorphan was the metabolite of dextromethorphan.","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14"},{"measure":"Time to Reach Cmax (Tmax) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14."},{"measure":"Tmax of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Paraxanthine on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14"},{"measure":"Tmax of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14"},{"measure":"Tmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Tmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUCinf of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Percent of AUC Extrapolated (AUC%Extrap) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"AUC%Extrap of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Apparent Terminal Elimination Rate Constant (Kel) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Kel of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Terminal Elimination Half-Life (T1/2) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14."},{"measure":"T1/2 of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14."},{"measure":"T1/2 of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. 5-OH Omeprazole was the metabolite of omeprazole.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"T1/2 of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Apparent Clearance (CL/F) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"CL/F of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Apparent Total Volume of Distribution Following Oral Administration (Vz/F) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Vz/F of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Percentage of Dose Recovered in Urine (Fe) for Losartan on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100.","timeFrame":"Predose, and 0 to 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Fe for E-3174 on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100. E-3174 was the metabolite of losartan.","timeFrame":"0 to 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Fe for Dextromethorphan on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100.","timeFrame":"0 to 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Fe for Dextrorphan on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100. Dextrorphan was the metabolite of dextromethorphan.","timeFrame":"0 to 8 hours postdose on Day -7, Day 1 and Day 14"},{"measure":"Cmax of Encorafenib on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14."},{"measure":"Cmax of LHY746 on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"Cmax of Binimetinib on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14."},{"measure":"Cmax of AR00426032 on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"AUClast of Encorafenib on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14."},{"measure":"AUClast of LHY746 on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"AUClast of Binimetinib on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"AUClast of AR00426032 on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"Tmax of Encorafenib on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14."},{"measure":"Tmax of LHY746 on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14"},{"measure":"Tmax of Binimetinib on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14."},{"measure":"Tmax of AR00426032 on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"AUCinf of Encorafenib on Day 1","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"AUCinf of Binimetinib on Day 1","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1."},{"measure":"AUCinf of AR00426032 on Day 1","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"T1/2 of Encorafenib on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"T1/2 of LHY746 on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"T1/2 of Binimetinib on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"T1/2 of AR00426032 on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14"},{"measure":"AUC%Extrap of Encorafenib on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"AUC%Extrap of LHY746 on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"AUC%Extrap of Binimetinib on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"AUC%Extrap of AR00426032 on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"Kel of Encorafenib on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"Kel of LHY746 on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"Kel of Binimetinib on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"Kel of AR00426032 on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1"},{"measure":"CL/F of Encorafenib on Day 1","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1."},{"measure":"CL/F of Binimetinib on Day 1","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1."},{"measure":"Vz/F of Encorafenib on Day 1","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1."},{"measure":"Vz/F of Binimetinib on Day 1","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1."},{"measure":"Cmax of Binimetinib on Day 14 and Day 21","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Cmax of AR00426032 on Day 14 and Day 21","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"AUClast of Binimetinib on Day 14 and Day 21","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"AUClast of AR00426032 on Day 14 and Day 21","description":"AUClast is AUC from time 0 (pre-dose) to the time of the last quantifiable concentration. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Tmax of Encorafenib on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Tmax of LHY746 on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Tmax of Binimetinib on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Tmax of AR00426032 on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"T1/2 of Encorafenib on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"T1/2 of LHY746 on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. LHY746 was the metabolite of encorafenib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"T1/2 of Binimetinib on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"T1/2 of AR00426032 on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. AR00426032 was the metabolite of binimetinib.","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21"},{"measure":"Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase","description":"An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of encorafenib/binimetinib and up to 30 days after treatment discontinuation. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase"},{"measure":"Number of Participants With Laboratory Abnormalities in the DDI Phase","description":"Laboratory parameters:hematology (hemoglobin,hematocrit,red blood cell \\[RBC\\],platelet,white blood cell count \\[WBC\\],neutrophils,eosinophils,monocytes, basophils, lymphocytes), chemistry (albumin, alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, bicarbonate, total bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lactate dehydrogenase, lipase, magnesium, inorganic phosphate, potassium, total protein, sodium, uric acid), urinalysis (appearance, color, specific gravity, pH, ketones, protein, glucose, blood, nitrates, leukocyte esterase, and urine microscopy results including WBC, RBC, bacteria, epithelial cells, and casts), coagulation (activated partial thromboplastin time, prothrombin time/international normalized ratio) and others. Clinically notable: worsening from baseline by at least 2 grades or to greater than or equal to (\\>=) Grade 3, by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase"},{"measure":"Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase","description":"Vital signs (temperature, pulse rate \\[PR\\]), systolic blood pressure \\[SBP\\]), and diastolic blood pressure \\[DBP\\]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP\\>=100 millimeters of mercury (mm Hg)/less than or equal to (\\<=) 50 mmHg with increase/decrease from baseline of \\>=15 mmHg; SBP: \\>=160 mmHg/\\<=90 mmHg with increase/decrease from baseline of \\>=20 mmHg; PR: \\>=120 beats per minute (bpm)/\\<=50 bpm with increase/decrease from baseline of \\>=15 bpm; temperature for Arms 1 and 3: \\>=37.5°C/\\<=35°C; Arms 2: \\>=37.5°C/\\<=36°C.","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase"},{"measure":"Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase","description":"Triplicate 12-lead ECG were performed after the participant had rested quietly for at least 10 minutes in a supine position. ECG parameters included RR interval, PR interval, QRS complex, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, Heart Rate and Fridericia's correction (QTcF) interval. The criterion included: QTcF \\>450 - \\<=480 mesc, \\>480 - \\<=500 msec, \\>500 msec, increase from baseline \\>30 - \\<=60 msec and increase from baseline \\>60 msec. QT interval \\>450 - \\<=480 msec, \\>480 - \\<=500 msec, \\>500 msec, increase from baseline \\>30 - \\<=60 msec and increase from baseline \\>60 msec. Heart rate increase from baseline \\>25% and value \\>100 bpm and decrease from baseline \\>25% and value \\<60 bpm. PR interval increase from baseline \\>25% and value \\>200 msec. QRS interval increase from baseline \\>25% and value \\>110 msec. Any new post-baseline notable ECG findings in the DDI phase was collected and reported in this outcome measure.","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase"},{"measure":"Number of Participants With Left Ventricular Ejection Fraction (LVEF) Abnormalities in the DDI Phase","description":"LVEF abnormalities are defined according to CTCAE grade version 4.03. Participants was considered as having a LVEF abnormality if the worst post-baseline value was Grade 2, 3, or 4 according to the following classification: Grade 0: Non-missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and \\<-20%; Grade 3: LVEF between 20% and 39% or absolute change from baseline lower than or equal to -20%; Grade 4: LVEF lower than 20%.","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase"},{"measure":"Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase","description":"An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of encorafenib/binimetinib and up to 30 days after treatment discontinuation. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. Any significant findings in the laboratory test, physical examinations, ophthalmic examinations, vital signs, ECG tests were captured as an AE.","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 up to 30 days after the post-DDI Phase"}]},"eligibilityModule":{"eligibilityCriteria":"Key Inclusion Criteria - Patients must meet all of the inclusion criteria to be eligible for enrollment into the study:\n\n* Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC or IV; or other BRAF V600-mutant advanced solid tumors\n* Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to enrollment, as determined using a local test;\n* Evidence of measurable or non-measurable lesions\n* Patient with unresectable locally advanced or metastatic melanoma who has received no prior treatment or progressed on or after prior systemic therapy; Note: Prior therapy with a BRAF proto-oncogene serine-threonine protein kinase (BRAF) inhibitor and/or a mitogen-activated protein (MAP) kinase (MEK) inhibitor is permitted except in the regimen immediately prior to study entry\n* Patient with other (non-melanoma) BRAF V600E and/or V600K -mutant advanced solid tumors who has progressed on standard therapy or for whom there are no available standard therapies; Note: Prior therapy with a BRAF inhibitor and/or a MEK inhibitor is permitted except in the regimen immediately prior to study entry\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1\n* Adequate bone marrow, hepatic and renal function as specified in the protocol\n* ARM 1 ONLY: Non-smoker who has not used nicotine containing products for at least 3 months prior to the first dose.\n\nKey Exclusion Criteria - Patients meeting any of the following criteria are not eligible for enrollment in the study:\n\n* Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable, with imaging (e.g., magnetic resonance imaging \\[MRI\\] or computed tomography \\[CT\\] demonstrating no current evidence of progressive brain metastases at screening);\n* Symptomatic or untreated leptomeningeal disease;\n* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);\n* Clinically significant cardiac disease\n* Known hyper-coagulability risks other than malignancy (e.g., Factor V Leiden syndrome);\n* Thromboembolic event except catheter-related venous thrombosis ≤ 12 weeks prior to starting study treatment.\n* Discontinuation of prior BRAF and/or MEK inhibitor treatment due to left ventricular dysfunction, pneumonitis/interstitial lung disease, or retinal vein occlusion;\n* ARM 1 ONLY: Positive urine cotinine test at screening\n* ARM 3 ONLY:\n\n  * History of psychosis, depression or mania;\n  * History of angioedema;\n  * History of mitral valve prolapse;\n  * History of left ventricular hypertrophy;","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Pfizer CT.gov Call Center","affiliation":"Pfizer","role":"STUDY_DIRECTOR"}],"locations":[{"facility":"UC Irvine Health","city":"Orange","state":"California","zip":"92868-3201","country":"United States","geoPoint":{"lat":33.78779,"lon":-117.85311}},{"facility":"University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)","city":"Aurora","state":"Colorado","zip":"80045","country":"United States","geoPoint":{"lat":39.72943,"lon":-104.83192}},{"facility":"University of Illinois at Chicago","city":"Chicago","state":"Illinois","zip":"60612","country":"United States","geoPoint":{"lat":41.85003,"lon":-87.65005}},{"facility":"Hopkins Eye Clinic","city":"Hopkins","state":"Minnesota","zip":"55343-8087","country":"United States","geoPoint":{"lat":44.92496,"lon":-93.46273}},{"facility":"Park Nicollet Eye Clinic","city":"Maple Grove","state":"Minnesota","zip":"55369","country":"United States","geoPoint":{"lat":45.07246,"lon":-93.45579}},{"facility":"Regions Cancer Care Center","city":"Saint Paul","state":"Minnesota","zip":"55101","country":"United States","geoPoint":{"lat":44.94441,"lon":-93.09327}},{"facility":"HealthPartners Specialty Center-Eye Care","city":"Saint Paul","state":"Minnesota","zip":"55130","country":"United States","geoPoint":{"lat":44.94441,"lon":-93.09327}},{"facility":"Gabrail Cancer Center Research","city":"Canton","state":"Ohio","zip":"44718","country":"United States","geoPoint":{"lat":40.79895,"lon":-81.37845}},{"facility":"University of TN Medical Center","city":"Knoxville","state":"Tennessee","zip":"37920","country":"United States","geoPoint":{"lat":35.96064,"lon":-83.92074}},{"facility":"Mary Crowley Cancer Research - Medical City Hospital","city":"Dallas","state":"Texas","zip":"75230","country":"United States","geoPoint":{"lat":32.78306,"lon":-96.80667}},{"facility":"Utah Cancer Specialists","city":"West Valley City","state":"Utah","zip":"84119","country":"United States","geoPoint":{"lat":40.69161,"lon":-112.00105}},{"facility":"Universitair Ziekenhuis Antwerpen","city":"Edegem","zip":"2650","country":"Belgium","geoPoint":{"lat":51.15662,"lon":4.44504}},{"facility":"Cross Cancer Institute","city":"Edmonton","state":"Alberta","zip":"T6G 1Z2","country":"Canada","geoPoint":{"lat":53.55014,"lon":-113.46871}},{"facility":"Princess Margaret Cancer Centre","city":"Toronto","state":"Ontario","zip":"M5G 2M9","country":"Canada","geoPoint":{"lat":43.70643,"lon":-79.39864}},{"facility":"Sir Mortimer B Davis Jewish General Hospital","city":"Montreal","state":"Quebec","zip":"H3T 1E2","country":"Canada","geoPoint":{"lat":45.50884,"lon":-73.58781}},{"facility":"McGill University Health Center","city":"Montreal","state":"Quebec","zip":"H4A 3J1","country":"Canada","geoPoint":{"lat":45.50884,"lon":-73.58781}},{"facility":"Jewish General Hospital","city":"Montrea","state":"Quebec","zip":"H3T 1E2","country":"Canada"},{"facility":"Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis","city":"Amsterdam","zip":"1066 CX","country":"Netherlands","geoPoint":{"lat":52.37403,"lon":4.88969}},{"facility":"Erasmus Medical Center","city":"Rotterdam","zip":"3000 CA","country":"Netherlands","geoPoint":{"lat":51.9225,"lon":4.47917}},{"facility":"Hospital del Mar","city":"Barcelona","zip":"08003","country":"Spain","geoPoint":{"lat":41.38879,"lon":2.15899}},{"facility":"Hospital Clinico Universitario Virgen de la Arrixaca","city":"El Palmar","zip":"30120","country":"Spain","geoPoint":{"lat":37.93939,"lon":-1.16095}},{"facility":"Hospital Universitari Arnau de Vilanova","city":"Lleida","zip":"25198","country":"Spain","geoPoint":{"lat":41.61674,"lon":0.62218}},{"facility":"Hospital Beata Maria Ana","city":"Madrid","zip":"28007","country":"Spain","geoPoint":{"lat":40.4165,"lon":-3.70256}},{"facility":"Hospital General Universitario Gregorio Marañon","city":"Madrid","zip":"28007","country":"Spain","geoPoint":{"lat":40.4165,"lon":-3.70256}},{"facility":"Clinica Rementeria","city":"Madrid","zip":"28010","country":"Spain","geoPoint":{"lat":40.4165,"lon":-3.70256}},{"facility":"MD Anderson Cancer Center Madrid","city":"Madrid","zip":"28033","country":"Spain","geoPoint":{"lat":40.4165,"lon":-3.70256}},{"facility":"Hospital Universitario HM Sanchinarro - CIOCC","city":"Madrid","zip":"28050","country":"Spain","geoPoint":{"lat":40.4165,"lon":-3.70256}},{"facility":"CERCO","city":"Seville","zip":"41009","country":"Spain","geoPoint":{"lat":37.38283,"lon":-5.97317}},{"facility":"Hospital Universitario Virgen Macarena","city":"Seville","zip":"41009","country":"Spain","geoPoint":{"lat":37.38283,"lon":-5.97317}}]},"referencesModule":{"references":[{"pmid":"38878209","type":"DERIVED","citation":"Piscitelli J, Reddy MB, Wollenberg L, Del Frari L, Gong J, Matschke K, Williams JH. Evaluation of the effect of modafinil on the pharmacokinetics of encorafenib and binimetinib in patients with BRAF V600-mutant advanced solid tumors. Cancer Chemother Pharmacol. 2024 Sep;94(3):337-347. doi: 10.1007/s00280-024-04676-2. Epub 2024 Jun 15."},{"pmid":"38424308","type":"DERIVED","citation":"Piscitelli J, Reddy MB, Wollenberg L, Del Frari L, Gong J, Wood L, Zhang Y, Matschke K, Williams JH. Clinical Evaluation of the Effect of Encorafenib on Bupropion, Rosuvastatin, and Coproporphyrin I and Considerations for Statin Coadministration. Clin Pharmacokinet. 2024 Apr;63(4):483-496. doi: 10.1007/s40262-024-01352-9. Epub 2024 Feb 29."}],"seeAlsoLinks":[{"label":"To obtain contact information for a study center near you, click here.","url":"https://pmiform.com/clinical-trial-info-request?StudyID=ARRAY-818-103"}]},"ipdSharingStatementModule":{"ipdSharing":"NO","description":"Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\\_trials/trial\\_data\\_and\\_results/data\\_requests."}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"This study was conducted in 3 Arms to evaluate the potential drug-drug interactions (DDIs) of single and multiple oral doses of encorafenib in combination with binimetinib with sensitive substrates of specific cytochrome P450 (CYP) enzymes (Arm 1), organic anion-transporting polypeptide (OATP)/breast cancer resistance protein (BCRP) transporters (Arm 2), and moderate CYP3A4 inducer (Arm 3). A total of 29, 12, 15 participants were enrolled in Arm 1, Arm 2, and Arm 3, respectively.","groups":[{"id":"FG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 milligrams \\[mg\\], dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg once daily \\[QD\\]) and binimetinib (tablet, 45 mg twice daily \\[BID\\]) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"FG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion immediate release (IR) tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"FG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"periods":[{"title":"DDI Phase","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"29"},{"groupId":"FG001","numSubjects":"12"},{"groupId":"FG002","numSubjects":"15"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"25"},{"groupId":"FG001","numSubjects":"12"},{"groupId":"FG002","numSubjects":"15"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]},{"type":"Physician Decision","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]},{"type":"Progressive Disease","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]}]},{"title":"Post-DDI Phase","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"25"},{"groupId":"FG001","numSubjects":"12"},{"groupId":"FG002","numSubjects":"15"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"25"},{"groupId":"FG001","numSubjects":"12"},{"groupId":"FG002","numSubjects":"15"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"5"},{"groupId":"FG001","numSubjects":"3"},{"groupId":"FG002","numSubjects":"2"}]},{"type":"Progressive Disease","reasons":[{"groupId":"FG000","numSubjects":"11"},{"groupId":"FG001","numSubjects":"6"},{"groupId":"FG002","numSubjects":"13"}]},{"type":"Discretion of investigator","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"1"},{"groupId":"FG002","numSubjects":"0"}]},{"type":"Study terminated by sponsor","reasons":[{"groupId":"FG000","numSubjects":"7"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]},{"type":"Withdrawal of consent","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"2"},{"groupId":"FG002","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"Safety analysis population who were treated with encorafenib-binimetinib.","groups":[{"id":"BG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"BG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"BG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met.continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"27"},{"groupId":"BG001","value":"12"},{"groupId":"BG002","value":"15"},{"groupId":"BG003","value":"54"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"Years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"62.3","spread":"12.14"},{"groupId":"BG001","value":"61.3","spread":"13.65"},{"groupId":"BG002","value":"58.9","spread":"9.98"},{"groupId":"BG003","value":"61.1","spread":"11.9"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"6"},{"groupId":"BG002","value":"7"},{"groupId":"BG003","value":"27"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"6"},{"groupId":"BG002","value":"8"},{"groupId":"BG003","value":"27"}]}]}]},{"title":"Race/Ethnicity, Customized","paramType":"NUMBER","unitOfMeasure":"Participants","classes":[{"title":"White","categories":[{"measurements":[{"groupId":"BG000","value":"25"},{"groupId":"BG001","value":"11"},{"groupId":"BG002","value":"14"},{"groupId":"BG003","value":"50"}]}]},{"title":"Black or African American","categories":[{"measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"1"}]}]},{"title":"Asian","categories":[{"measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"},{"groupId":"BG003","value":"2"}]}]},{"title":"Other","categories":[{"measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"1"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline pharmacokinetic (PK) sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"nanograms per milliliter (ng/mL)","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"9.45","spread":"45.1"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"11.1","spread":"50.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.44","spread":"54.6"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.17","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.978","ciUpperLimit":"1.40","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.258","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.215","ciUpperLimit":"0.308","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"45.2","spread":"31.5"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"50.5","spread":"40.8"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"56.7","spread":"27.7"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.12","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.998","ciUpperLimit":"1.25","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.25","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.12","ciUpperLimit":"1.40","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"3.36","spread":"53.4"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"4.52","spread":"52.7"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.09","spread":"71.6"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.34","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.12","ciUpperLimit":"1.62","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.622","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.517","ciUpperLimit":"0.748","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"41.5","spread":"32.8"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"45.4","spread":"43.7"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"54.1","spread":"29.1"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.09","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.975","ciUpperLimit":"1.23","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.30","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.16","ciUpperLimit":"1.46","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1150","spread":"31.5"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1210","spread":"30.6"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1300","spread":"19.8"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.05","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.922","ciUpperLimit":"1.20","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.13","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.992","ciUpperLimit":"1.29","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"984","spread":"37.2"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1070","spread":"40.4"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1110","spread":"29.7"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.09","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.990","ciUpperLimit":"1.19","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.10","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.00","ciUpperLimit":"1.22","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"357","spread":"41.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"319","spread":"27.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"247","spread":"53.5"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.894","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.741","ciUpperLimit":"1.08","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.692","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.573","ciUpperLimit":"0.835","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"267","spread":"188.7"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"354","spread":"73.1"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"271","spread":"57.1"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.32","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.861","ciUpperLimit":"2.04","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.01","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.659","ciUpperLimit":"1.56","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"91.8","spread":"104.5"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"90.4","spread":"79.3"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"64.4","spread":"54.8"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.01","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.762","ciUpperLimit":"1.33","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.718","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.543","ciUpperLimit":"0.948","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"6.98","spread":"96.4"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"30.3","spread":"130.8"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"18.7","spread":"113.7"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"4.34","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"2.94","ciUpperLimit":"6.40","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"2.68","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.82","ciUpperLimit":"3.96","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"94.0","spread":"63.9"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"70.9","spread":"50.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"71.0","spread":"52.7"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.754","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.595","ciUpperLimit":"0.954","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.755","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.596","ciUpperLimit":"0.957","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"181","spread":"46.9"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"189","spread":"49.7"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"256","spread":"62.5"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.05","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.864","ciUpperLimit":"1.27","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.42","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.17","ciUpperLimit":"1.72","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Area Under the Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Plasma Midazolam on Day -7, Day 1, and Day 14","description":"AUClast is area under the concentration-time profile (AUC) from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"nanograms*hour per milliliter (ng*hr/mL)","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"25.7","spread":"57.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"27.6","spread":"58.4"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"4.52","spread":"52.9"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.07","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.920","ciUpperLimit":"1.25","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.175","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.151","ciUpperLimit":"0.204","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"135","spread":"29.9"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"173","spread":"41.8"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"142","spread":"38.9"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.28","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.18","ciUpperLimit":"1.38","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.05","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.974","ciUpperLimit":"1.14","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"8.87","spread":"43.7"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"11.1","spread":"46.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"4.55","spread":"62.6"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.25","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.09","ciUpperLimit":"1.43","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.513","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.449","ciUpperLimit":"0.587","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"125","spread":"32.0"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"160","spread":"44.5"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"133","spread":"41.0"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.28","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.17","ciUpperLimit":"1.39","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.07","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.979","ciUpperLimit":"1.16","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5940","spread":"35.8"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"6480","spread":"34.4"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"7520","spread":"22.7"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.09","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.947","ciUpperLimit":"1.26","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.27","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.10","ciUpperLimit":"1.46","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5100","spread":"36.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5700","spread":"45.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"6430","spread":"29.6"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.12","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.02","ciUpperLimit":"1.23","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.26","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.14","ciUpperLimit":"1.38","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Paraxanthine was the metabolite of caffeine.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2160","spread":"47.7"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1940","spread":"31.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1470","spread":"64.6"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.900","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.721","ciUpperLimit":"1.12","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.679","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.544","ciUpperLimit":"0.848","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"815","spread":"193.3"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"1020","spread":"91.9"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"674","spread":"54.3"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.26","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.800","ciUpperLimit":"1.98","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.827","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.526","ciUpperLimit":"1.30","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"313","spread":"134.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"302","spread":"92.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"195","spread":"60.6"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.980","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.688","ciUpperLimit":"1.39","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.633","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.445","ciUpperLimit":"0.900","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"33.6","spread":"88.1"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"93.8","spread":"97.9"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"52.8","spread":"66.3"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"2.79","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"2.08","ciUpperLimit":"3.74","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.57","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.17","ciUpperLimit":"2.11","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"339","spread":"48.1"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"261","spread":"49.0"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"250","spread":"50.1"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.769","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.637","ciUpperLimit":"0.928","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.736","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.610","ciUpperLimit":"0.889","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Hydroxybupropion was the metabolite of bupropion.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1090","spread":"59.8"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"1080","spread":"63.8"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1610","spread":"65.7"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.993","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.803","ciUpperLimit":"1.23","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.48","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.20","ciUpperLimit":"1.83","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"milligrams (mg)","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.239","spread":"268.0"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.349","spread":"314.2"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.286","spread":"277.3"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.45","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.902","ciUpperLimit":"2.32","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.18","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.720","ciUpperLimit":"1.93","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Ae0-8 of E-3174 on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. E-3174 was the metabolite of losartan.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"mg","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.227","spread":"293.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.332","spread":"276.2"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.205","spread":"317.8"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.47","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.915","ciUpperLimit":"2.36","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.851","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.519","ciUpperLimit":"1.39","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"mg","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0264","spread":"396.7"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0323","spread":"542.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0225","spread":"899.2"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.20","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.775","ciUpperLimit":"1.87","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.940","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.593","ciUpperLimit":"1.49","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. Dextrorphan was the metabolite of dextromethorphan.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"mg","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.78","spread":"183.9"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"4.41","spread":"165.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.55","spread":"222.5"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.18","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.830","ciUpperLimit":"1.67","estimateComment":"Day 1 / Day -7"},{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.979","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.680","ciUpperLimit":"1.41","estimateComment":"Day 14 / Day -7"}]},{"type":"PRIMARY","title":"Cmax of Plasma Encorafenib on Day 14 and Day 21 in Arm 3","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3540","spread":"55.6"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"2830","spread":"67.2"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.798","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.585","ciUpperLimit":"1.09","estimateComment":"Day 21 / Day 14"}]},{"type":"PRIMARY","title":"Cmax of Plasma LHY746 on Day 14 and Day 21 in Arm 3","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2460","spread":"24.7"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"2510","spread":"26.8"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.02","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.935","ciUpperLimit":"1.11","estimateComment":"Day 21 / Day 14"}]},{"type":"PRIMARY","title":"AUClast of Plasma Encorafenib on Day 14 and Day 21 in Arm 3","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"11900","spread":"35.8"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"9100","spread":"30.3"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"0.762","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.613","ciUpperLimit":"0.945","estimateComment":"Day 21 / Day 14"}]},{"type":"PRIMARY","title":"AUClast of Plasma LHY746 on Day 14 and Day 21 in Arm 3","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"31100","spread":"45.4"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"33100","spread":"31.2"}]}]}],"analyses":[{"groupIds":["OG000"],"nonInferiorityType":"OTHER","paramType":"Geometric LS Mean Ratio","paramValue":"1.06","ciPctValue":"90","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.929","ciUpperLimit":"1.22","estimateComment":"Day 21 / Day 14"}]},{"type":"SECONDARY","title":"Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight (MW), which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. 1-OH midazolam was the metabolite of midazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"5.00","spread":"63.3"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"5.97","spread":"72.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"30.1","spread":"65.7"}]}]}]},{"type":"SECONDARY","title":"Ratio of AUC From Time Zero Extrapolated to Infinity (AUCinf) Values of the Metabolite Compared to Parent (MRAUCinf) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14","description":"MRAUCinf is the ratio of AUCinf values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUCinf (metabolite) × MW (parent)\\] / \\[AUCinf (parent) × MW (metabolite)\\]. 1-OH midazolam was the metabolite of midazolam. AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"16"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"4.31","spread":"68.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5.21","spread":"87.8"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"29.5","spread":"70.3"}]}]}]},{"type":"SECONDARY","title":"MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. Paraxanthine was the metabolite of caffeine.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.392","spread":"37.2"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.324","spread":"44.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.211","spread":"72.3"}]}]}]},{"type":"SECONDARY","title":"MRAUClast for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.309","spread":"107.2"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.282","spread":"87.0"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.277","spread":"44.6"}]}]}]},{"type":"SECONDARY","title":"MRAUCinf for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14","description":"MRAUCinf is the ratio of AUCinf values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUCinf (metabolite) × MW (parent)\\] / \\[AUCinf (parent) × MW (metabolite)\\]. 5-OH Omeprazole was the metabolite of omeprazole. AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"5"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.312","spread":"119.8"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.960","spread":"92.6"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.312","spread":"49.8"}]}]}]},{"type":"SECONDARY","title":"MRAUClast for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. Hydroxybupropion was the metabolite of bupropion.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"3.01","spread":"60.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"3.88","spread":"47.5"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"6.04","spread":"57.5"}]}]}]},{"type":"SECONDARY","title":"MRAUClast for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21","description":"MRAUClast is the ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[AUClast (metabolite) × MW (parent)\\] / \\[AUClast (parent) × MW (metabolite)\\]. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3.31","spread":"58.9"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"4.62","spread":"43.3"}]}]}]},{"type":"SECONDARY","title":"Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. 1-OH midazolam was the metabolite of midazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"4.56","spread":"54.7"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"4.36","spread":"62.8"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"22.2","spread":"60.6"}]}]}]},{"type":"SECONDARY","title":"MRCmax for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. Paraxanthine was the metabolite of caffeine.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.335","spread":"25.4"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.285","spread":"36.8"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.205","spread":"54.9"}]}]}]},{"type":"SECONDARY","title":"MRCmax for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"0.273","spread":"115.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.244","spread":"83.0"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.227","spread":"48.2"}]}]}]},{"type":"SECONDARY","title":"MRCmax for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. Hydroxybupropion was the metabolite of bupropion.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1.80","spread":"61.1"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"2.51","spread":"50.0"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3.38","spread":"48.8"}]}]}]},{"type":"SECONDARY","title":"MRCmax for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21","description":"MRCmax is the ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, which was calculated by \\[Cmax (metabolite) × MW (parent)\\] / \\[Cmax (parent) × MW (metabolite)\\]. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.883","spread":"72.5"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"1.13","spread":"77.6"}]}]}]},{"type":"SECONDARY","title":"Ratio of Ae0-8 Values of the Metabolite Compared to Parent (MRAe0-8) for E-3174/Losartan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. MRAe0-8 is the ratio of Ae0-8 values of the metabolite compared to parent, corrected for molecular weight. E-3174 was the metabolite of losartan.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.920","spread":"65.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.921","spread":"100.0"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.693","spread":"99.0"}]}]}]},{"type":"SECONDARY","title":"MRAe0-8 for Dextrorphan/Dextromethorphan on Day -7, Day 1 and Day 14","description":"Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. MRAe0-8 is the ratio of Ae0-8 values of the metabolite compared to parent, corrected for molecular weight. Dextrorphan was the metabolite of dextromethorphan.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Ratio","timeFrame":"0 to 8 hours after dosing on Days -7, 1 and 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"151","spread":"383.2"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"144","spread":"560.9"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"167","spread":"354.5"}]}]}]},{"type":"SECONDARY","title":"Time to Reach Cmax (Tmax) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.77","upperLimit":"2.93"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.88","lowerLimit":"0.77","upperLimit":"1.30"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.88","lowerLimit":"0.68","upperLimit":"1.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.77","upperLimit":"2.93"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.90","lowerLimit":"0.80","upperLimit":"1.85"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.88","lowerLimit":"0.68","upperLimit":"1.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.77","upperLimit":"2.93"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.90","lowerLimit":"0.80","upperLimit":"1.85"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.92","lowerLimit":"0.68","upperLimit":"1.72"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.77","upperLimit":"2.97"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.90","lowerLimit":"0.80","upperLimit":"1.83"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.88","lowerLimit":"0.68","upperLimit":"1.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.80","upperLimit":"1.98"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.93","lowerLimit":"0.78","upperLimit":"1.88"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.90","lowerLimit":"0.72","upperLimit":"2.92"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.80","upperLimit":"2.17"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.94","lowerLimit":"0.78","upperLimit":"1.88"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.98","lowerLimit":"0.72","upperLimit":"3.97"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Paraxanthine on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"7.18","lowerLimit":"3.77","upperLimit":"7.98"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"7.63","lowerLimit":"1.83","upperLimit":"7.92"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"6.00","lowerLimit":"2.13","upperLimit":"8.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"2.20","lowerLimit":"1.05","upperLimit":"8.07"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"3.00","lowerLimit":"0.87","upperLimit":"7.92"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3.00","lowerLimit":"0.85","upperLimit":"7.85"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"2.97","lowerLimit":"0.00","upperLimit":"8.07"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"3.80","lowerLimit":"0.87","upperLimit":"7.92"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3.00","lowerLimit":"0.85","upperLimit":"7.85"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"2.40","lowerLimit":"1.00","upperLimit":"4.02"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"1.85","lowerLimit":"0.78","upperLimit":"7.00"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1.40","lowerLimit":"0.92","upperLimit":"3.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"1.87","lowerLimit":"0.82","upperLimit":"4.00"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"1.93","lowerLimit":"0.77","upperLimit":"4.00"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1.92","lowerLimit":"0.93","upperLimit":"2.87"}]}]}]},{"type":"SECONDARY","title":"Tmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"4.00","lowerLimit":"3.00","upperLimit":"8.00"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"7.68","lowerLimit":"3.83","upperLimit":"8.00"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3.94","lowerLimit":"1.00","upperLimit":"6.17"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"27.1","spread":"72.5"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"27.1","spread":"65.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5.10","spread":"52.5"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"16"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"150","spread":"27.7"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"172","spread":"49.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"154","spread":"35.5"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"9.98","spread":"43.9"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"13.1","spread":"44.9"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5.52","spread":"56.2"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"139","spread":"30.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"167","spread":"52.4"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"143","spread":"36.3"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1630","spread":"151.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"5"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1170","spread":"79.4"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"904","spread":"35.7"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"5"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"557","spread":"92.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"880","spread":"21.8"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"294","spread":"44.5"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"75.4","spread":"62.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"139","spread":"69.8"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"62.9","spread":"48.5"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"6"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"398","spread":"54.9"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"390","spread":"11.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"298","spread":"38.4"}]}]}]},{"type":"SECONDARY","title":"Percent of AUC Extrapolated (AUC%Extrap) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"19.1","spread":"46.0"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"19.3","spread":"37.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"8.76","spread":"55.2"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"15.2","spread":"35.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"21.9","spread":"40.1"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"12.6","spread":"68.4"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"14.1","spread":"42.6"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"12.9","spread":"46.1"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"12.8","spread":"68.1"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"15.3","spread":"35.0"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"22.6","spread":"40.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"14.1","spread":"54.9"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"48.3","spread":"39.4"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"53.2","spread":"27.0"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"61.0","spread":"26.0"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"16"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"46.7","spread":"37.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"54.8","spread":"25.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"58.0","spread":"25.3"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"7.35","spread":"142.1"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"11.9","spread":"141.2"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"4.22","spread":"113.9"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"12.4","spread":"147.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"26.1","spread":"65.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"8.07","spread":"66.7"}]}]}]},{"type":"SECONDARY","title":"Apparent Terminal Elimination Rate Constant (Kel) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"0.196","spread":"26.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.188","spread":"22.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.347","spread":"55.4"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"0.248","spread":"20.1"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.199","spread":"31.3"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.259","spread":"36.9"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"0.231","spread":"24.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"0.236","spread":"31.1"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"0.269","spread":"47.2"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.241","spread":"23.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.197","spread":"32.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.277","spread":"37.7"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0870","spread":"57.4"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0753","spread":"61.3"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0575","spread":"61.7"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"16"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0893","spread":"70.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0739","spread":"58.3"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0656","spread":"54.4"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.401","spread":"50.4"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.296","spread":"53.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.461","spread":"31.1"}]}]}]},{"type":"SECONDARY","title":"Kel of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.303","spread":"43.1"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.197","spread":"45.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.386","spread":"22.5"}]}]}]},{"type":"SECONDARY","title":"Terminal Elimination Half-Life (T1/2) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"3.54","spread":"26.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"3.69","spread":"22.6"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.00","spread":"55.4"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"2.80","spread":"20.1"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"3.48","spread":"31.3"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.68","spread":"36.9"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","categories":[{"measurements":[{"groupId":"OG000","value":"3.00","spread":"24.2"}]}]},{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"2.93","spread":"31.1"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.58","spread":"47.2"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.87","spread":"23.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.53","spread":"32.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.50","spread":"37.7"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"7.97","spread":"57.4"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"9.20","spread":"61.3"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"12.1","spread":"61.7"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \\[predose concentration\\*e\\^(-Kel\\*t)\\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"16"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"7.76","spread":"70.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"9.38","spread":"58.3"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"10.6","spread":"54.4"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.73","spread":"50.4"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.34","spread":"53.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.50","spread":"31.1"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. 5-OH Omeprazole was the metabolite of omeprazole.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.29","spread":"43.1"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.53","spread":"45.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.80","spread":"22.5"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Rosuvastatin on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"5"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.25","spread":"51.8"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.13","spread":"17.0"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.86","spread":"23.0"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Plasma Bupropion on Day -7, Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 2 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.81","spread":"15.1"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.24","spread":"10.2"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.75","spread":"15.2"}]}]}]},{"type":"SECONDARY","title":"Apparent Clearance (CL/F) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Liters (L)/hour (h)","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"73.9","spread":"72.5"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"73.9","spread":"65.1"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"392","spread":"52.5"}]}]}]},{"type":"SECONDARY","title":"CL/F of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"L/h","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"12.3","spread":"151.6"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"5"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"17.0","spread":"79.4"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"22.1","spread":"35.7"}]}]}]},{"type":"SECONDARY","title":"Apparent Total Volume of Distribution Following Oral Administration (Vz/F) of Plasma Midazolam on Day -7, Day 1 and Day 14","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Litre","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"306","spread":"67.7"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"339","spread":"54.6"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1030","spread":"54.7"}]}]}]},{"type":"SECONDARY","title":"Vz/F of Plasma Omeprazole on Day -7, Day 1 and Day 14","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Litre","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"29.1","spread":"93.9"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"5"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"44.6","spread":"63.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"45.9","spread":"39.3"}]}]}]},{"type":"SECONDARY","title":"Percentage of Dose Recovered in Urine (Fe) for Losartan on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of dose","timeFrame":"Predose, and 0 to 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.478","spread":"268.0"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.699","spread":"314.2"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.572","spread":"277.3"}]}]}]},{"type":"SECONDARY","title":"Fe for E-3174 on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100. E-3174 was the metabolite of losartan.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of dose","timeFrame":"0 to 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.440","spread":"293.3"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.644","spread":"276.2"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.396","spread":"317.8"}]}]}]},{"type":"SECONDARY","title":"Fe for Dextromethorphan on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of dose","timeFrame":"0 to 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0881","spread":"396.7"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.108","spread":"542.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0.0750","spread":"899.2"}]}]}]},{"type":"SECONDARY","title":"Fe for Dextrorphan on Day -7, Day 1 and Day 14","description":"Fe is the percentage of dose recovered in urine from 0 to 8 hours as parent or metabolite, which was calculated as Ae0-8 / dose × 100. Dextrorphan was the metabolite of dextromethorphan.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days -7, 1, and 14. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of dose","timeFrame":"0 to 8 hours postdose on Day -7, Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"title":"Day -7","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"13.3","spread":"183.9"}]}]},{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"18"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"15.6","spread":"165.5"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"12.5","spread":"222.5"}]}]}]},{"type":"SECONDARY","title":"Cmax of Encorafenib on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"6150","spread":"41.9"},{"groupId":"OG001","value":"6060","spread":"77.7"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3240","spread":"55.7"},{"groupId":"OG001","value":"2940","spread":"72.2"}]}]}]},{"type":"SECONDARY","title":"Cmax of LHY746 on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"943","spread":"66.6"},{"groupId":"OG001","value":"953","spread":"66.0"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2490","spread":"32.4"},{"groupId":"OG001","value":"2340","spread":"66.8"}]}]}]},{"type":"SECONDARY","title":"Cmax of Binimetinib on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"661","spread":"55.1"},{"groupId":"OG001","value":"549","spread":"89.5"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"521","spread":"59.9"},{"groupId":"OG001","value":"566","spread":"63.1"}]}]}]},{"type":"SECONDARY","title":"Cmax of AR00426032 on Day 1 and Day 14","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"57.0","spread":"41.2"},{"groupId":"OG001","value":"63.3","spread":"73.2"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"23.3","spread":"85.6"},{"groupId":"OG001","value":"27.4","spread":"43.1"}]}]}]},{"type":"SECONDARY","title":"AUClast of Encorafenib on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"24500","spread":"36.7"},{"groupId":"OG001","value":"25900","spread":"61.7"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"12700","spread":"37.6"},{"groupId":"OG001","value":"13100","spread":"28.6"}]}]}]},{"type":"SECONDARY","title":"AUClast of LHY746 on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"5130","spread":"66.1"},{"groupId":"OG001","value":"4990","spread":"78.1"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"34000","spread":"34.4"},{"groupId":"OG001","value":"32800","spread":"54.5"}]}]}]},{"type":"SECONDARY","title":"AUClast of Binimetinib on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"2290","spread":"43.3"},{"groupId":"OG001","value":"2040","spread":"81.0"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2190","spread":"33.8"},{"groupId":"OG001","value":"2210","spread":"40.7"}]}]}]},{"type":"SECONDARY","title":"AUClast of AR00426032 on Day 1 and Day 14","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"236","spread":"39.6"},{"groupId":"OG001","value":"256","spread":"74.8"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"108","spread":"74.1"},{"groupId":"OG001","value":"122","spread":"67.4"}]}]}]},{"type":"SECONDARY","title":"Tmax of Encorafenib on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"2.00","lowerLimit":"1.00","upperLimit":"5.92"},{"groupId":"OG001","value":"1.87","lowerLimit":"0.85","upperLimit":"3.98"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1.94","lowerLimit":"0.82","upperLimit":"3.02"},{"groupId":"OG001","value":"1.93","lowerLimit":"1.00","upperLimit":"4.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of LHY746 on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"6.93","lowerLimit":"2.07","upperLimit":"8.07"},{"groupId":"OG001","value":"7.42","lowerLimit":"3.00","upperLimit":"8.00"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.98","lowerLimit":"1.80","upperLimit":"8.22"},{"groupId":"OG001","value":"3.47","lowerLimit":"1.85","upperLimit":"6.25"}]}]}]},{"type":"SECONDARY","title":"Tmax of Binimetinib on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"1.97","lowerLimit":"0.87","upperLimit":"4.03"},{"groupId":"OG001","value":"1.97","lowerLimit":"0.85","upperLimit":"4.08"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1.98","lowerLimit":"0.97","upperLimit":"3.02"},{"groupId":"OG001","value":"1.93","lowerLimit":"1.02","upperLimit":"2.92"}]}]}]},{"type":"SECONDARY","title":"Tmax of AR00426032 on Day 1 and Day 14","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","categories":[{"measurements":[{"groupId":"OG000","value":"2.02","lowerLimit":"0.98","upperLimit":"4.03"},{"groupId":"OG001","value":"2.48","lowerLimit":"1.82","upperLimit":"6.13"}]}]},{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.00","lowerLimit":"0.98","upperLimit":"3.02"},{"groupId":"OG001","value":"2.00","lowerLimit":"1.00","upperLimit":"2.92"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Encorafenib on Day 1","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"3"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"26200","spread":"71.6"},{"groupId":"OG001","value":"45100","spread":"56.8"}]}]}]},{"type":"SECONDARY","title":"AUCinf of Binimetinib on Day 1","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"},{"groupId":"OG001","value":"6"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"2970","spread":"45.4"},{"groupId":"OG001","value":"3280","spread":"47.7"}]}]}]},{"type":"SECONDARY","title":"AUCinf of AR00426032 on Day 1","description":"AUCinf is AUC from time zero to extrapolated infinite time. It is obtained by AUClast + (Clast/kel), where AUClast is the AUC from time zero to the time of last quantifiable concentration (Clast), and kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number of analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"},{"groupId":"OG001","value":"2"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"270","spread":"40.5"},{"groupId":"OG001","value":"432","spread":"32.4"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Encorafenib on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"},{"groupId":"OG001","value":"7"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.98","spread":"46.4"},{"groupId":"OG001","value":"3.77","spread":"37.0"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"4.37","spread":"42.7"},{"groupId":"OG001","value":"3.58","spread":"13.7"}]}]}]},{"type":"SECONDARY","title":"T1/2 of LHY746 on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"1"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"9.47","spread":"130.1"},{"groupId":"OG001","value":"22.5","spread":"NA","comment":"Data was not reported as only 1 participant was analyzed for this arm."}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"},{"groupId":"OG001","value":"6"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"9.27","spread":"40.0"},{"groupId":"OG001","value":"11.2","spread":"20.6"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Binimetinib on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"},{"groupId":"OG001","value":"6"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.62","spread":"35.4"},{"groupId":"OG001","value":"2.45","spread":"17.3"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"},{"groupId":"OG001","value":"10"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.90","spread":"39.9"},{"groupId":"OG001","value":"3.70","spread":"42.8"}]}]}]},{"type":"SECONDARY","title":"T1/2 of AR00426032 on Day 1 and Day 14","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arms 1 and 2 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 1 and 14. Number of participants analyzed represents the total number of participants in each arm in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"20"},{"groupId":"OG001","value":"10"}]}],"classes":[{"title":"Day 1","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"},{"groupId":"OG001","value":"6"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2.96","spread":"23.3"},{"groupId":"OG001","value":"3.15","spread":"24.7"}]}]},{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"16"},{"groupId":"OG001","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"3.97","spread":"42.6"},{"groupId":"OG001","value":"3.89","spread":"51.9"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Encorafenib on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"24.4","spread":"73.9"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of LHY746 on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"52.9","spread":"56.1"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of Binimetinib on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"13.7","spread":"60.2"}]}]}]},{"type":"SECONDARY","title":"AUC%Extrap of AR00426032 on Day 1","description":"AUC%extrap is the percentage of AUCinf obtained by forward extrapolation. It is calculated as (AUCinf minus AUClast)\\*100/ AUCinf. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Percentage of AUC","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"19.8","spread":"33.8"}]}]}]},{"type":"SECONDARY","title":"Kel of Encorafenib on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.174","spread":"46.4"}]}]}]},{"type":"SECONDARY","title":"Kel of LHY746 on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"2"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.0732","spread":"130.1"}]}]}]},{"type":"SECONDARY","title":"Kel of Binimetinib on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.265","spread":"35.4"}]}]}]},{"type":"SECONDARY","title":"Kel of AR00426032 on Day 1","description":"Kel is the apparent terminal elimination rate constant, which is estimated by linear regression of time versus loge concentration. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Fraction/hour","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.234","spread":"23.3"}]}]}]},{"type":"SECONDARY","title":"CL/F of Encorafenib on Day 1","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"L/h","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"17.2","spread":"71.6"}]}]}]},{"type":"SECONDARY","title":"CL/F of Binimetinib on Day 1","description":"CL/F is the apparent total body clearance of drug from the plasma (parent drugs only), which is estimated by Dose / AUCinf (Day -7) or Dose / AUClast (Day 1 and Day 14).","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"L/h","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"15.1","spread":"45.4"}]}]}]},{"type":"SECONDARY","title":"Vz/F of Encorafenib on Day 1","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the total number of participants in Arm 1 in the evaluable PK set. Number of analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Litre","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"53.4","spread":"38.2"}]}]}]},{"type":"SECONDARY","title":"Vz/F of Binimetinib on Day 1","description":"Vz/F is the apparent volume of distribution during the terminal phase (parent drugs only), which is calculated by CL/F/kel.","populationDescription":"All participants in Arm 1 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Day 1. Number of participants analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Litre","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"47.6","spread":"50.5"}]}]}]},{"type":"SECONDARY","title":"Cmax of Binimetinib on Day 14 and Day 21","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"660","spread":"39.7"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"663","spread":"25.3"}]}]}]},{"type":"SECONDARY","title":"Cmax of AR00426032 on Day 14 and Day 21","description":"Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"25.9","spread":"63.2"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"24.7","spread":"36.7"}]}]}]},{"type":"SECONDARY","title":"AUClast of Binimetinib on Day 14 and Day 21","description":"AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2400","spread":"38.6"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"2290","spread":"30.6"}]}]}]},{"type":"SECONDARY","title":"AUClast of AR00426032 on Day 14 and Day 21","description":"AUClast is AUC from time 0 (pre-dose) to the time of the last quantifiable concentration. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"ng*hr/mL","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"114","spread":"64.5"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"112","spread":"33.0"}]}]}]},{"type":"SECONDARY","title":"Tmax of Encorafenib on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.88","upperLimit":"2.03"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.98","upperLimit":"3.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of LHY746 on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.05","lowerLimit":"1.00","upperLimit":"6.00"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"2.10","lowerLimit":"1.00","upperLimit":"6.00"}]}]}]},{"type":"SECONDARY","title":"Tmax of Binimetinib on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.88","upperLimit":"3.00"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"1.00","lowerLimit":"0.95","upperLimit":"2.10"}]}]}]},{"type":"SECONDARY","title":"Tmax of AR00426032 on Day 14 and Day 21","description":"Tmax is time to reach maximum observed plasma concentration. It was observed directly from the concentration-time data. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Full Range","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"2.00","lowerLimit":"0.88","upperLimit":"3.00"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"2.00","lowerLimit":"0.95","upperLimit":"2.23"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Encorafenib on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"3.48","spread":"26.6"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"3.57","spread":"27.3"}]}]}]},{"type":"SECONDARY","title":"T1/2 of LHY746 on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. LHY746 was the metabolite of encorafenib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"8.67","spread":"33.1"}]}]},{"title":"Day 21","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"8.01","spread":"18.8"}]}]}]},{"type":"SECONDARY","title":"T1/2 of Binimetinib on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"4.62","spread":"42.1"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"4.55","spread":"44.8"}]}]}]},{"type":"SECONDARY","title":"T1/2 of AR00426032 on Day 14 and Day 21","description":"T1/2 is the terminal elimination half-life, which is estimated by Loge(2) / kel, where kel is the apparent terminal elimination rate constant. AR00426032 was the metabolite of binimetinib.","populationDescription":"All participants in Arm 3 who received at least 1 dose of any study intervention and had at least 1 post-baseline PK sample with an associated bioanalytical result, and who were with sufficient concentration data to calculate at least 1 PK parameter on Days 14 and 21. Number of participants analyzed represents the total number of participants in Arm 3 in the evaluable PK set. Number analyzed represents the number of participants who had reportable parameter values.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Geometric Coefficient of Variation","unitOfMeasure":"Hours","timeFrame":"Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21","groups":[{"id":"OG000","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"}]}],"classes":[{"title":"Day 14","categories":[{"measurements":[{"groupId":"OG000","value":"5.60","spread":"37.1"}]}]},{"title":"Day 21","categories":[{"measurements":[{"groupId":"OG000","value":"5.22","spread":"58.7"}]}]}]},{"type":"SECONDARY","title":"Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase","description":"An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of encorafenib/binimetinib and up to 30 days after treatment discontinuation. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.","populationDescription":"All participants who received at least 1 dose of encorafenib/binimetinib.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Count of Participants","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail (DDI Phase)","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion (DDI Phase)","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG002","title":"Arm 3 - Modafinil (DDI Phase)","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"classes":[{"title":"Participants with all-causality TEAEs","categories":[{"measurements":[{"groupId":"OG000","value":"26"},{"groupId":"OG001","value":"9"},{"groupId":"OG002","value":"11"}]}]},{"title":"Participants with treatment-related TEAEs","categories":[{"measurements":[{"groupId":"OG000","value":"24"},{"groupId":"OG001","value":"6"},{"groupId":"OG002","value":"10"}]}]},{"title":"Participants with all-causality SAEs","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]},{"title":"Participants with treatment-related SAEs","categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs leading to study drug discontinuation (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs leading to study drug discontinuation (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs requiring dose interruption (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"4"},{"groupId":"OG002","value":"4"}]}]},{"title":"AEs requiring dose interruption (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"2"}]}]},{"title":"AEs requiring dose reduction (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs requiring dose reduction (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs requiring additional therapy (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"10"}]}]},{"title":"AEs requiring additional therapy (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"6"},{"groupId":"OG002","value":"8"}]}]},{"title":"Deaths","categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]}]},{"type":"SECONDARY","title":"Number of Participants With Laboratory Abnormalities in the DDI Phase","description":"Laboratory parameters:hematology (hemoglobin,hematocrit,red blood cell \\[RBC\\],platelet,white blood cell count \\[WBC\\],neutrophils,eosinophils,monocytes, basophils, lymphocytes), chemistry (albumin, alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, bicarbonate, total bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lactate dehydrogenase, lipase, magnesium, inorganic phosphate, potassium, total protein, sodium, uric acid), urinalysis (appearance, color, specific gravity, pH, ketones, protein, glucose, blood, nitrates, leukocyte esterase, and urine microscopy results including WBC, RBC, bacteria, epithelial cells, and casts), coagulation (activated partial thromboplastin time, prothrombin time/international normalized ratio) and others. Clinically notable: worsening from baseline by at least 2 grades or to greater than or equal to (\\>=) Grade 3, by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.","populationDescription":"All participants who received at least 1 dose of encorafenib/binimetinib.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Count of Participants","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"classes":[{"title":"Hemoglobin CTCAE Graded Low","categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]},{"title":"Lymphocytes CTCAE Graded Low","categories":[{"measurements":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"Lymphocytes CTCAE Graded High","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"Neutrophils CTCAE Graded Low","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]},{"title":"Amylase CTCAE Graded High","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"Creatinine CTCAE Graded High","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"3"}]}]},{"title":"Glucose CTCAE Graded High","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"1"}]}]},{"title":"Lipase CTCAE Graded High","categories":[{"measurements":[{"groupId":"OG000","value":"7"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"Glucose CTCAE Graded Low","categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"1"}]}]},{"title":"Creatine Kinase CTCAE Graded High","categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]}]},{"type":"SECONDARY","title":"Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase","description":"Vital signs (temperature, pulse rate \\[PR\\]), systolic blood pressure \\[SBP\\]), and diastolic blood pressure \\[DBP\\]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP\\>=100 millimeters of mercury (mm Hg)/less than or equal to (\\<=) 50 mmHg with increase/decrease from baseline of \\>=15 mmHg; SBP: \\>=160 mmHg/\\<=90 mmHg with increase/decrease from baseline of \\>=20 mmHg; PR: \\>=120 beats per minute (bpm)/\\<=50 bpm with increase/decrease from baseline of \\>=15 bpm; temperature for Arms 1 and 3: \\>=37.5°C/\\<=35°C; Arms 2: \\>=37.5°C/\\<=36°C.","populationDescription":"All participants who received at least 1 dose of encorafenib/binimetinib.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Count of Participants","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"classes":[{"title":"SBP high (>=160mmHg with increase from baseline of >=20mmHg)","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"4"},{"groupId":"OG002","value":"0"}]}]},{"title":"SBP low (<=90mmHg with decrease from baseline of >=20mmHg)","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"DBP high (>=100mmHg with increase from baseline of >=15mmHg)","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"DBP low (<=50mmHg with decrease from baseline of >=15mmHg)","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"PR high (>=120bpm with increase from baseline of >=15bpm)","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]},{"title":"PR low (<=50bpm with decrease from baseline of >=15bpm）","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"Temperature high","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"10"},{"groupId":"OG002","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"Temperature low","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"10"},{"groupId":"OG002","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"1"}]}]}]},{"type":"SECONDARY","title":"Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase","description":"Triplicate 12-lead ECG were performed after the participant had rested quietly for at least 10 minutes in a supine position. ECG parameters included RR interval, PR interval, QRS complex, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, Heart Rate and Fridericia's correction (QTcF) interval. The criterion included: QTcF \\>450 - \\<=480 mesc, \\>480 - \\<=500 msec, \\>500 msec, increase from baseline \\>30 - \\<=60 msec and increase from baseline \\>60 msec. QT interval \\>450 - \\<=480 msec, \\>480 - \\<=500 msec, \\>500 msec, increase from baseline \\>30 - \\<=60 msec and increase from baseline \\>60 msec. Heart rate increase from baseline \\>25% and value \\>100 bpm and decrease from baseline \\>25% and value \\<60 bpm. PR interval increase from baseline \\>25% and value \\>200 msec. QRS interval increase from baseline \\>25% and value \\>110 msec. Any new post-baseline notable ECG findings in the DDI phase was collected and reported in this outcome measure.","populationDescription":"All participants who received at least 1 dose of encorafenib/binimetinib. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Count of Participants","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"classes":[{"title":"New QTcF >450 - <=480 mesc","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"23"},{"groupId":"OG001","value":"11"},{"groupId":"OG002","value":"13"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"2"}]}]},{"title":"New QTcF >480 - <=500 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"11"},{"groupId":"OG002","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"New QTcF >500 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]},{"title":"New QTcF Increase from baseline >30 - <=60 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"5"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"2"}]}]},{"title":"New QTcF Increase from baseline >60 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"New QT >450 - <=480 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"26"},{"groupId":"OG001","value":"10"},{"groupId":"OG002","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"4"}]}]},{"title":"New QT >480 - <=500 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"1"}]}]},{"title":"New QT >500 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"14"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"New QT Increase from baseline >30 - <=60 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"5"},{"groupId":"OG002","value":"9"}]}]},{"title":"New QT Increase from baseline >60 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"New Heart rate Increase from baseline >25% and value >100 bpm","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"New Heart rate Decrease from baseline >25% and value <60 bpm","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"New PR Increase from baseline >25% and value >200 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"26"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"3"}]}]},{"title":"New QRS Increase from baseline >25% and value >110 msec","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"0"}]}]}]},{"type":"SECONDARY","title":"Number of Participants With Left Ventricular Ejection Fraction (LVEF) Abnormalities in the DDI Phase","description":"LVEF abnormalities are defined according to CTCAE grade version 4.03. Participants was considered as having a LVEF abnormality if the worst post-baseline value was Grade 2, 3, or 4 according to the following classification: Grade 0: Non-missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and \\<-20%; Grade 3: LVEF between 20% and 39% or absolute change from baseline lower than or equal to -20%; Grade 4: LVEF lower than 20%.","populationDescription":"All participants who received at least 1 dose of encorafenib/binimetinib.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Count of Participants","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All drugs were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]}]},{"type":"SECONDARY","title":"Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase","description":"An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of encorafenib/binimetinib and up to 30 days after treatment discontinuation. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. Any significant findings in the laboratory test, physical examinations, ophthalmic examinations, vital signs, ECG tests were captured as an AE.","populationDescription":"All participants who received at least 1 dose of encorafenib/binimetinib.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Count of Participants","timeFrame":"After 1st dose of encorafenib/binimetinib on Day 1 up to 30 days after the post-DDI Phase","groups":[{"id":"OG000","title":"Arm 1 - CYP Probe Cocktail","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 milligrams \\[mg\\], dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg once daily \\[QD\\]) and binimetinib (tablet, 45 mg twice daily \\[BID\\]) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG001","title":"Arm 2 - Rosuvastatin and Bupropion","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion immediate release (IR) tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28)."},{"id":"OG002","title":"Arm 3 - Modafinil","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"25"},{"groupId":"OG001","value":"12"},{"groupId":"OG002","value":"15"}]}],"classes":[{"title":"Participants with all-causality TEAEs","categories":[{"measurements":[{"groupId":"OG000","value":"17"},{"groupId":"OG001","value":"5"},{"groupId":"OG002","value":"4"}]}]},{"title":"Participants with treatment-related TEAEs","categories":[{"measurements":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"2"}]}]},{"title":"Participants with all-causality SAEs","categories":[{"measurements":[{"groupId":"OG000","value":"11"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"4"}]}]},{"title":"Participants with treatment-related SAEs","categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"AEs leading to study drug discontinuation (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"2"}]}]},{"title":"AEs leading to study drug discontinuation (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"1"}]}]},{"title":"AEs requiring dose interruption (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"1"}]}]},{"title":"AEs requiring dose interruption (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"7"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"1"}]}]},{"title":"AEs requiring dose reduction (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs requiring dose reduction (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"title":"AEs requiring additional therapy (all-causality)","categories":[{"measurements":[{"groupId":"OG000","value":"14"},{"groupId":"OG001","value":"4"},{"groupId":"OG002","value":"2"}]}]},{"title":"AEs requiring additional therapy (treatment-related)","categories":[{"measurements":[{"groupId":"OG000","value":"7"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"0"}]}]},{"title":"Deaths","categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"1"},{"groupId":"OG002","value":"3"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 and up to Day 28 visit for Arm 1, Arm 2 and Arm 3. Post-DDI phase was the period after the 1st dose of encorafenib-binimetinib on Day 1 up to 167.0 weeks for Arm 1, up to 48.1 weeks for Arm 2 and 67.9 weeks for Arm 3","description":"An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both serious and non-serious event. Safety population included all participants who received at least one dose of encorafenib and/or binimetinib.","eventGroups":[{"id":"EG000","title":"Arm 1 - CYP Probe Cocktail (DDI Phase)","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).","deathsNumAffected":0,"deathsNumAtRisk":27,"seriousNumAffected":2,"seriousNumAtRisk":27,"otherNumAffected":25,"otherNumAtRisk":27},{"id":"EG001","title":"Arm 2 - Rosuvastatin and Bupropion (DDI Phase)","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).","deathsNumAffected":0,"deathsNumAtRisk":12,"seriousNumAffected":1,"seriousNumAtRisk":12,"otherNumAffected":9,"otherNumAtRisk":12},{"id":"EG002","title":"Arm 3 - Modafinil (DDI Phase)","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).","deathsNumAffected":0,"deathsNumAtRisk":15,"seriousNumAffected":0,"seriousNumAtRisk":15,"otherNumAffected":11,"otherNumAtRisk":15},{"id":"EG003","title":"Arm 1 - CYP Probe Cocktail （Post-DDI Phase)","description":"Participants received a single oral dose of the CYP probe cocktail (losartan tablet 25 mg, dextromethorphan capsule 30 mg, caffeine liquid 50 mg, omeprazole capsule 20 mg, and midazolam syrup 2 mg) on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).","deathsNumAffected":1,"deathsNumAtRisk":25,"seriousNumAffected":11,"seriousNumAtRisk":25,"otherNumAffected":4,"otherNumAtRisk":25},{"id":"EG004","title":"Arm 2 - Rosuvastatin and Bupropion (Post-DDI Phase)","description":"Participants received a single oral dose of rosuvastatin tablet 10 mg and bupropion IR tablet 75 mg on Day -7, Day 1, and Day 14. Encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) were continuously administered initiated on Day 1 until treatment discontinuation criteria were met. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 35 days (Day -7 to Day 28).","deathsNumAffected":2,"deathsNumAtRisk":12,"seriousNumAffected":3,"seriousNumAtRisk":12,"otherNumAffected":4,"otherNumAtRisk":12},{"id":"EG005","title":"Arm 3 - Modafinil (Post-DDI Phase)","description":"Participants received continuous treatment with encorafenib (capsule, 450 mg QD) and binimetinib (tablet, 45 mg BID) from Day 1 until treatment discontinuation criteria were met. Continuous treatment of modafinil (tablet, 400 mg QD) was started on Day 15 through Day 21. All study interventions were taken within 10 minutes. There were 2 treatment phases, a DDI phase followed by a post-DDI phase. The duration of the DDI phase was 28 days (Day 1 to Day 28).","deathsNumAffected":3,"deathsNumAtRisk":15,"seriousNumAffected":4,"seriousNumAtRisk":15,"otherNumAffected":3,"otherNumAtRisk":15}],"seriousEvents":[{"term":"Seizure","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA version 26.0","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":27},{"groupId":"EG001","numAffected":0,"numAtRisk":12},{"groupId":"EG002","numAffected":0,"numAtRisk":15},{"groupId":"EG003","numAffected":0,"numAtRisk":25},{"groupId":"EG004","numAffected":0,"numAtRisk":12},{"groupId":"EG005","numAffected":1,"numAtRisk":15}]},{"term":"Metastases to central nervous system","organSystem":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","sourceVocabulary":"MedDRA version 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