{"protocolSection":{"identificationModule":{"nctId":"NCT02209597","orgStudyIdInfo":{"id":"201312021"},"organization":{"fullName":"Washington University School of Medicine","class":"OTHER"},"briefTitle":"Clinical Study of Generic and Brand Bupropion in Depression","officialTitle":"Bioequivalence and Clinical Effects of Generic and Brand Bupropion","acronym":"BALANCE"},"statusModule":{"statusVerifiedDate":"2020-04","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2014-06-25","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2016-08-14","type":"ACTUAL"},"completionDateStruct":{"date":"2016-08-14","type":"ACTUAL"},"studyFirstSubmitDate":"2014-07-07","studyFirstSubmitQcDate":"2014-08-04","studyFirstPostDateStruct":{"date":"2014-08-06","type":"ESTIMATED"},"resultsFirstSubmitDate":"2018-06-20","resultsFirstSubmitQcDate":"2020-04-23","resultsFirstPostDateStruct":{"date":"2020-04-24","type":"ACTUAL"},"lastUpdateSubmitDate":"2020-04-23","lastUpdatePostDateStruct":{"date":"2020-04-24","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Washington University School of Medicine","class":"OTHER"}},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":true},"descriptionModule":{"briefSummary":"Determine bioequivalence between branded and generic bupropion extended release (XL) products (and between generic products) at steady state in patients with major depressive disorder.","detailedDescription":"The protocol is a prospective, randomized, double-blinded, crossover study with Major Depressive Disorder (MDD) receiving bupropion HCl 300mg XL (branded or generic).\n\nSubjects will be studied in 4 phases for a total of approximately 28 weeks:\n\nPhase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics)."},"conditionsModule":{"conditions":["Major Depressive Disorder"],"keywords":["Major Depressive Disorder","bupropion XL","Wellbutrin XL"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"SEQUENTIAL","interventionModelDescription":"Each participant receives the 4 drugs in sequence (sequence is randomized).","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"DOUBLE","maskingDescription":"The randomization table will be generated by the Barnes-Jewish Hospital Investigational Pharmacy. Each subject will be assigned the next available number. Subjects, investigators, and all study team members will be blinded to drug treatment. In the case of dropouts (either subject- or investigator-initiated), subjects will be replaced, to provide the required number of subjects.","whoMasked":["PARTICIPANT","CARE_PROVIDER"]}},"enrollmentInfo":{"count":74,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"StudyArm","type":"EXPERIMENTAL","description":"Subjects will be studied for 28 weeks in a sequential cross-over study: a\n\nSubjects will be studied in 4 phases for a total of approximately 28 weeks:\n\nPhase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).","interventionNames":["Drug: Bupropion XL 300"]}],"interventions":[{"type":"DRUG","name":"Bupropion XL 300","description":"Subjects will be studied in 4 phases for a total of approximately 28 weeks:\n\nPhase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).","armGroupLabels":["StudyArm"],"otherNames":["Wellbutrin","Par","Mylan","Valeant"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion","description":"Area under the curve (AUC) generic/Area under the curve (AUC) brand bupropion","timeFrame":"For 24 hours approximately every 6 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria\n\nEach subject must meet all of the following criteria:\n\n1. Adult outpatients age 18-75 years\n2. Currently on once daily bupropion HCl 300mg XL (brand or any generic), for a minimum of 4 months\n3. Major depressive disorder (MDD), in partial or full remission for at least 4 months, as confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Spontaneous relapse of depression unrelated to medication changes is less likely - about 5% chance per year - after remission has been maintained for at least 4 months.2\n4. Ability to understand and willingness to comply with study procedures, and to provide written informed consent\n\nExclusion Criteria\n\nSubjects will not be enrolled if any of the following criteria exist:\n\n1. Remission from depression not clearly attributed to bupropion treatment\n2. Current severe side effects attributable to bupropion\n3. Poor adherence to bupropion treatment per patient self- report and history of refill persistence\n4. History of active seizure disorder, or seizure treatment within past year\n5. History of significant hepatic or renal disease, based on physician assessment\n6. Currently taking drugs or natural products known to influence cytochrome P450B6 (CYP2B6) activity\n7. Currently taking drugs for hepatitis C or multiple sclerosis, due to their ability to cause depression\n8. Dementia or other significant cognitive impairment, per diagnosis or investigative team's assessment\n9. Lifetime diagnosis of schizophrenia, schizoaffective or schizophreniform dis-order, delusional disorder, or current psychotic symptoms diagnosed by SCID\n10. Abuse of or dependence on alcohol or other substances within the past 6 months as determined by SCID, and confirmed by study physician interview\n11. Current suicidal ideation","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"75 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Evan D Kharasch, MD, PhD","affiliation":"Washington Univesity School of Medicine","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Washington University School of Medicine","city":"St Louis","state":"Missouri","zip":"63110","country":"United States","geoPoint":{"lat":38.62727,"lon":-90.19789}}]},"referencesModule":{"references":[{"pmid":"38467432","type":"DERIVED","citation":"Kharasch ED, Lenze EJ. Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion. Drug Metab Dispos. 2024 Apr 16;52(5):455-466. doi: 10.1124/dmd.124.001697."}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Bupropion","description":"Phase 1: (Non-randomized) an approximately 4-week lead-in phase during which participants remain on their existing bupropion product\n\nOther Names:\n\nWellbutrin Par Mylan Valeant"}],"periods":[{"title":"Phase 1 Current Tx (Non-randomized)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"74"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"71"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"2"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"1"}]}]},{"title":"Phase 2 (Randomized: 1 Brand, 3 Generic)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"71"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"67"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"4"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"3"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"1"}]}]},{"title":"Phase 3 (Randomized: 1 Brand, 3 Generic)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"67"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"67"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"}]}]},{"title":"Phase 4 (Randomized: 1 Brand, 3 Generic)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"67"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"67"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Bupropion","description":"Subjects will be studied for 28 weeks in a sequential cross-over study:\n\n1. a 4-week lead-in phase during which all participants remain on their existing bupropion product\n2. Four randomized cross-over phases of 6 weeks on each of the four bupropion study drugs (brand Wellbutrin 300mg XL, Valeant, Par and Watson 3 generics)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"70"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEDIAN","dispersionType":"INTER_QUARTILE_RANGE","unitOfMeasure":"years","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"70"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"47","lowerLimit":"37","upperLimit":"57"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"70"}]}],"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"53"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"17"}]}]}]},{"title":"Race and Ethnicity Not Collected","populationDescription":"Race and Ethnicity were not collected from any participant.","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion","description":"Area under the curve (AUC) generic/Area under the curve (AUC) brand bupropion","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Full Range","unitOfMeasure":"percentage of Brand","timeFrame":"For 24 hours approximately every 6 weeks","groups":[{"id":"OG000","title":"Valeant Brand Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics)."},{"id":"OG001","title":"Par Generic Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics)."},{"id":"OG002","title":"Watson Generic Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics)."},{"id":"OG003","title":"Mylan Generic Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"67"},{"groupId":"OG001","value":"67"},{"groupId":"OG002","value":"67"},{"groupId":"OG003","value":"67"}]}],"classes":[{"title":"Bupropion","categories":[{"measurements":[{"groupId":"OG000","value":".84","lowerLimit":".71","upperLimit":"1.04"},{"groupId":"OG001","value":".88","lowerLimit":".72","upperLimit":"1.08"},{"groupId":"OG002","value":".83","lowerLimit":".68","upperLimit":".99"},{"groupId":"OG003","value":".89","lowerLimit":".7","upperLimit":"1.06"}]}]},{"title":"Hydroxybupropion","categories":[{"measurements":[{"groupId":"OG000","value":"20.9","lowerLimit":"15.5","upperLimit":"25.5"},{"groupId":"OG001","value":"20.9","lowerLimit":"15.9","upperLimit":"28.1"},{"groupId":"OG002","value":"21.8","lowerLimit":"15.9","upperLimit":"26.5"},{"groupId":"OG003","value":"21.6","lowerLimit":"15.9","upperLimit":"27.7"}]}]},{"title":"Erthrohydrobuprion","categories":[{"measurements":[{"groupId":"OG000","value":"2.09","lowerLimit":"1.52","upperLimit":"2.59"},{"groupId":"OG001","value":"2.05","lowerLimit":"1.47","upperLimit":"2.57"},{"groupId":"OG002","value":"1.98","lowerLimit":"1.48","upperLimit":"2.34"},{"groupId":"OG003","value":"2.02","lowerLimit":"1.61","upperLimit":"2.50"}]}]},{"title":"Threohydrobupropion","categories":[{"measurements":[{"groupId":"OG000","value":"9.38","lowerLimit":"7.21","upperLimit":"13.27"},{"groupId":"OG001","value":"9.05","lowerLimit":"7.21","upperLimit":"13.27"},{"groupId":"OG002","value":"8.57","lowerLimit":"6.83","upperLimit":"11.57"},{"groupId":"OG003","value":"8.78","lowerLimit":"7.25","upperLimit":"12.49"}]}]}],"analyses":[{"groupIds":["OG000","OG001","OG002","OG003"],"nonInferiorityType":"SUPERIORITY","pValue":"<0.05","statisticalMethod":"ANOVA","ciPctValue":"90","ciNumSides":"ONE_SIDED"}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"28 weeks","eventGroups":[{"id":"EG000","title":"Valeant Brand Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).","deathsNumAffected":0,"deathsNumAtRisk":71,"seriousNumAffected":0,"seriousNumAtRisk":71,"otherNumAffected":0,"otherNumAtRisk":71},{"id":"EG001","title":"PAR Generic Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).","deathsNumAffected":0,"deathsNumAtRisk":71,"seriousNumAffected":0,"seriousNumAtRisk":71,"otherNumAffected":0,"otherNumAtRisk":71},{"id":"EG002","title":"Watson Generic Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).","deathsNumAffected":0,"deathsNumAtRisk":71,"seriousNumAffected":0,"seriousNumAtRisk":71,"otherNumAffected":1,"otherNumAtRisk":71},{"id":"EG003","title":"Mylan Generic Bupropion XL® 300mg","description":"Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).","deathsNumAffected":0,"deathsNumAtRisk":71,"seriousNumAffected":0,"seriousNumAtRisk":71,"otherNumAffected":0,"otherNumAtRisk":71}],"otherEvents":[{"term":"depression","organSystem":"Nervous system disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":71},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":71},{"groupId":"EG002","numEvents":1,"numAffected":1,"numAtRisk":71},{"groupId":"EG003","numEvents":0,"numAffected":0,"numAtRisk":71}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Evan Kharasch MD PhD","organization":"Washington University","email":"kharasch@wustl.edu","phone":"3143628796"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2015-11-19","uploadDate":"2020-03-18T12:26","filename":"Prot_SAP_000.pdf","size":548894}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D003865","term":"Depressive Disorder, Major"}],"ancestors":[{"id":"D003866","term":"Depressive Disorder"},{"id":"D019964","term":"Mood Disorders"},{"id":"D001523","term":"Mental Disorders"}]},"interventionBrowseModule":{"meshes":[{"id":"D016642","term":"Bupropion"},{"id":"D000077297","term":"Pregnane X Receptor"}],"ancestors":[{"id":"D011427","term":"Propiophenones"},{"id":"D007659","term":"Ketones"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D011987","term":"Receptors, Steroid"},{"id":"D018160","term":"Receptors, Cytoplasmic and Nuclear"},{"id":"D011506","term":"Proteins"},{"id":"D000602","term":"Amino Acids, Peptides, and Proteins"},{"id":"D014157","term":"Transcription Factors"}]}},"hasResults":true}