{"protocolSection":{"identificationModule":{"nctId":"NCT01111539","orgStudyIdInfo":{"id":"31-08-255"},"secondaryIdInfos":[{"id":"2010-018796-21","type":"EUDRACT_NUMBER"}],"organization":{"fullName":"Otsuka Pharmaceutical Development & Commercialization, Inc.","class":"INDUSTRY"},"briefTitle":"Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)","officialTitle":"A Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Patients With Major Depressive Disorder"},"statusModule":{"statusVerifiedDate":"2021-09","overallStatus":"TERMINATED","whyStopped":"The study was terminated early due to Sponsor decision, closure of this combination therapy program is unrelated to any safety issues, no signals of concern.","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2010-07-13","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2011-09-20","type":"ACTUAL"},"completionDateStruct":{"date":"2011-09-20","type":"ACTUAL"},"studyFirstSubmitDate":"2010-04-22","studyFirstSubmitQcDate":"2010-04-26","studyFirstPostDateStruct":{"date":"2010-04-27","type":"ESTIMATED"},"resultsFirstSubmitDate":"2021-09-28","resultsFirstSubmitQcDate":"2021-09-28","resultsFirstPostDateStruct":{"date":"2021-10-20","type":"ACTUAL"},"dispFirstSubmitDate":"2012-08-17","dispFirstSubmitQcDate":"2012-08-24","dispFirstPostDateStruct":{"date":"2012-08-31","type":"ESTIMATED"},"lastUpdateSubmitDate":"2021-09-28","lastUpdatePostDateStruct":{"date":"2021-10-20","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc.","class":"INDUSTRY"}},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false},"descriptionModule":{"briefSummary":"This will be a multicenter, randomized, double-blind study designed to assess the efficacy, safety and tolerability of an oral Aripiprazole/Escitalopram combination therapy in participants with MDD who have demonstrated an incomplete response to a prospective trial of Escitalopram, and report a treatment history for the current MDD episode of an inadequate response to at least one and no more than three adequate trials of an approved antidepressant other than Escitalopram. An inadequate response is defined as less than a 50% reduction in depressive symptom severity as assessed by the participant's self-report on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ) and evaluated by the investigator as part of the participant's medical and psychiatric history. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration (or at least 3 weeks for combination treatments) at an approved dose as specified in the ATRQ.","detailedDescription":"The study will be organized as follows:\n\n* Screening Phase\n* Single-blind Prospective Treatment Phase\n* Single-blind Continuation Phase (Responder) or Double-blind Randomization Phase (non-Responder)\n* 30 day Post Treatment Follow-up\n\nAssigned Interventions:\n\n* Escitalopram monotherapy\n* Aripiprazole/Escitalopram combination therapy\n* Aripiprazole monotherapy"},"conditionsModule":{"conditions":["Major Depressive Disorder (MDD)"],"keywords":["Major Depressive Disorder","MDD","Depression"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"DOUBLE","whoMasked":["PARTICIPANT","INVESTIGATOR"]}},"enrollmentInfo":{"count":211,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Phase B: Single-blind Prospective Treatment Phase","type":"EXPERIMENTAL","description":"Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.","interventionNames":["Drug: Escitalopram","Drug: Blinded capsule"]},{"label":"Phase B+: Single-blind Phase B Responders","type":"EXPERIMENTAL","description":"Participants with response (≥50% reduction in depressive symptom severity in Hamilton Depression Rating Scale {HAM-D17} Total Score; or a HAM-D17 Total Score of \\<14 at Week 8 or a Clinical Global Impression of Improvement {CGI-I} Score of \\<3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B, for up to maximum of Week 14, in Phase B+.","interventionNames":["Drug: Escitalopram","Drug: Blinded capsule"]},{"label":"Phase C: Aripiprazole/Escitalopram Combination","type":"EXPERIMENTAL","description":"Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.","interventionNames":["Drug: Escitalopram","Drug: Aripiprazole","Drug: Blinded capsule"]},{"label":"Phase C: Escitalopram Monotherapy","type":"EXPERIMENTAL","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.","interventionNames":["Drug: Escitalopram","Drug: Blinded capsule"]},{"label":"Phase C: Aripiprazole Monotherapy","type":"EXPERIMENTAL","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability.","interventionNames":["Drug: Aripiprazole","Drug: Blinded capsule"]}],"interventions":[{"type":"DRUG","name":"Escitalopram","description":"Escitalopram capsule administered orally, once daily without regard to meals.","armGroupLabels":["Phase B+: Single-blind Phase B Responders","Phase B: Single-blind Prospective Treatment Phase","Phase C: Aripiprazole/Escitalopram Combination","Phase C: Escitalopram Monotherapy"]},{"type":"DRUG","name":"Aripiprazole","description":"Aripiprazole capsule administered orally, once daily without regard to meals.","armGroupLabels":["Phase C: Aripiprazole Monotherapy","Phase C: Aripiprazole/Escitalopram Combination"]},{"type":"DRUG","name":"Blinded capsule","description":"Blinded capsule administered orally, once daily.","armGroupLabels":["Phase B+: Single-blind Phase B Responders","Phase B: Single-blind Prospective Treatment Phase","Phase C: Aripiprazole Monotherapy","Phase C: Aripiprazole/Escitalopram Combination","Phase C: Escitalopram Monotherapy"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)","description":"The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change from Week 8 indicates improvement.","timeFrame":"Week 8 to Week 14"}],"secondaryOutcomes":[{"measure":"Phase C: Mean Clinical Global Impression - Improvement (CGI-I) Scale Score at the End of Phase C (Week 14)","description":"CGI-I is a 7-point clinician-rated scale ranging from 1 to 7, rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A higher score indicates greater impairment.","timeFrame":"Week 14"},{"measure":"Phase C: Mean Change From End of Phase B (Week 8) in the Sheehan Disability Scale (SDS) Mean Score to End of Phase C (Week 14)","description":"SDS is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change from Week 8 indicates improvement.","timeFrame":"Week 8 to Week 14"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Participants with a current diagnosis of a major depressive episode. The current depressive episode must be ≥8 weeks in duration\n* Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period\n* Participants with a Hamilton Depression Rating Scale (HAM-D17) Total Score ≥18 at the Baseline Visit for the Prospective Treatment Phase\n\nExclusion Criteria:\n\n* Lack of prior treatment with an antidepressant during the current depressive episode\n* Participants who report treatment with adjunctive or monotherapy antipsychotic treatment during the current depressive episode\n* Participants experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode\n* Participants with epilepsy or significant history of seizure disorders\n* Participants with a clinically significant current diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder\n* Participants who have received electroconvulsive therapy (ECT) in the last 10 years","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"65 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"locations":[{"city":"Cerritos","state":"California","zip":"90703","country":"United States","geoPoint":{"lat":33.85835,"lon":-118.06479}},{"city":"Costa Mesa","state":"California","zip":"92626","country":"United States","geoPoint":{"lat":33.64113,"lon":-117.91867}},{"city":"Irvine","state":"California","zip":"92618","country":"United States","geoPoint":{"lat":33.66946,"lon":-117.82311}},{"city":"San Diego","state":"California","zip":"92102","country":"United States","geoPoint":{"lat":32.71571,"lon":-117.16472}},{"city":"Santa Ana","state":"California","zip":"92705","country":"United States","geoPoint":{"lat":33.74557,"lon":-117.86783}},{"city":"Denver","state":"Colorado","zip":"80204","country":"United 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researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.","infoTypes":["STUDY_PROTOCOL","SAP","CSR"],"timeFrame":"Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.","accessCriteria":"Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/","url":"https://clinical-trials.otsuka.com"}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"A total of 211 participants were enrolled in Phase B (Single-blind Prospective Treatment Phase) to receive escitalopram monotherapy(10 or 20mg/day),of which 45 responders continued to Phase B+(Single-blind Phase B Responders),received escitalopram monotherapy(10 or 20mg/day),84 non-responders were randomized in 1:1:1 ratio to Phase C(Double-blind Randomization Phase),received aripiprazole/escitalopram combination therapy or escitalopram or aripiprazole monotherapy.","recruitmentDetails":"Participants took part in the study at 69 investigative sites in Estonia, Finland, Germany, India, Italy, Mexico, South Korea, Taiwan, Ukraine, and the United States from 13 July 2010 to 20 September 2011.","groups":[{"id":"FG000","title":"Phase B: Single-blind Prospective Treatment Phase","description":"Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+."},{"id":"FG001","title":"Phase B+: Single-blind Phase B Responders","description":"Participants with response (≥50% reduction in depressive symptom severity in Hamilton Depression Rating Scale {HAM-D17} Total Score; or a HAM-D17 Total Score of \\<14 at Week 8 or a Clinical Global Impression of Improvement {CGI-I} Score of \\<3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B, for up to maximum of Week 14, in Phase B+."},{"id":"FG002","title":"Phase C: Aripiprazole/Escitalopram Combination","description":"Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C."},{"id":"FG003","title":"Phase C: Escitalopram Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C."},{"id":"FG004","title":"Phase C: Aripiprazole Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability."}],"periods":[{"title":"Phase B (Day 1 to Week 8)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"211"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"129"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"82"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]}],"dropWithdraws":[{"type":"Lost to 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record.","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"45"},{"groupId":"FG002","numSubjects":"28"},{"groupId":"FG003","numSubjects":"27"},{"groupId":"FG004","numSubjects":"28"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"38"},{"groupId":"FG002","numSubjects":"22"},{"groupId":"FG003","numSubjects":"20"},{"groupId":"FG004","numSubjects":"18"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"7"},{"groupId":"FG002","numSubjects":"6"},{"groupId":"FG003","numSubjects":"8"},{"groupId":"FG004","numSubjects":"10"}]}],"dropWithdraws":[{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"1"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"1"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"1"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"2"}]},{"type":"Sponsor Discontinued Study","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"7"},{"groupId":"FG002","numSubjects":"4"},{"groupId":"FG003","numSubjects":"5"},{"groupId":"FG004","numSubjects":"5"}]},{"type":"Subject Met Withdrawal Criteria","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"1"}]},{"type":"Investigator Withdrew Subject","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"1"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"Subject Withdrew Consent","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"2"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"Protocol Deviation","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"1"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record.","groups":[{"id":"BG000","title":"Phase B: Single-blind Prospective Treatment Phase","description":"Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+."}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"44.4","spread":"11.1"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"140"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"71"}]}]}]},{"title":"Ethnicity (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Hispanic or Latino","measurements":[{"groupId":"BG000","value":"42"}]},{"title":"Not Hispanic or Latino","measurements":[{"groupId":"BG000","value":"168"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"1"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"16"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"36"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"23"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"130"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"6"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)","description":"The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change from Week 8 indicates improvement.","populationDescription":"ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind study medication and had at least one post-randomization efficacy evaluation.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"score on a scale","timeFrame":"Week 8 to Week 14","groups":[{"id":"OG000","title":"Phase C: Aripiprazole/Escitalopram Combination","description":"Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C."},{"id":"OG001","title":"Phase C: Escitalopram Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C."},{"id":"OG002","title":"Phase C: Aripiprazole Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"28"},{"groupId":"OG001","value":"27"},{"groupId":"OG002","value":"28"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-8.0","spread":"1.5"},{"groupId":"OG001","value":"-7.0","spread":"1.5"},{"groupId":"OG002","value":"-4.3","spread":"1.5"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"The statistical analyses was performed by fitting an analysis of covariance (ANCOVA) model to the change from baseline data (Week 8 Visit) for the MADRS Total Score at the Week 14 visit (LOCF). The model included baseline MADRS Total Score as a covariate and treatment as the main effect.","nonInferiorityType":"SUPERIORITY","pValue":"=0.644","statisticalMethod":"ANCOVA","paramType":"Treatment Difference","paramValue":"-1.0","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-5.2","ciUpperLimit":"3.3"},{"groupIds":["OG000","OG002"],"groupDescription":"The statistical analyses will be performed by fitting an ANCOVA model to the change from baseline data (Week 8 Visit) for the MADRS Total Score at the Week 14 visit (LOCF). The model will include baseline MADRS Total Score as a covariate and treatment as the main effect.","nonInferiorityType":"SUPERIORITY","pValue":"=0.080","statisticalMethod":"ANCOVA","paramType":"Treatment Difference","paramValue":"-3.7","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-7.8","ciUpperLimit":"0.4"}]},{"type":"SECONDARY","title":"Phase C: Mean Clinical Global Impression - Improvement (CGI-I) Scale Score at the End of Phase C (Week 14)","description":"CGI-I is a 7-point clinician-rated scale ranging from 1 to 7, rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A higher score indicates greater impairment.","populationDescription":"ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind study medication and had at least one post-randomization efficacy evaluation.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"score on a scale","timeFrame":"Week 14","groups":[{"id":"OG000","title":"Phase C: Aripiprazole/Escitalopram Combination","description":"Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C."},{"id":"OG001","title":"Phase C: Escitalopram Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C."},{"id":"OG002","title":"Phase C: Aripiprazole Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"28"},{"groupId":"OG001","value":"27"},{"groupId":"OG002","value":"28"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"2.6","spread":"0.2"},{"groupId":"OG001","value":"2.9","spread":"0.2"},{"groupId":"OG002","value":"3.0","spread":"0.1"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"=0.366","statisticalMethod":"Cochran-Mantel-Haenszel","paramType":"Treatment Difference","paramValue":"-0.3","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-0.8","ciUpperLimit":"0.3"},{"groupIds":["OG000","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"=0.138","statisticalMethod":"Cochran-Mantel-Haenszel","paramType":"Treatment Difference","paramValue":"-0.4","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-0.9","ciUpperLimit":"0.1"}]},{"type":"SECONDARY","title":"Phase C: Mean Change From End of Phase B (Week 8) in the Sheehan Disability Scale (SDS) Mean Score to End of Phase C (Week 14)","description":"SDS is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change from Week 8 indicates improvement.","populationDescription":"ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind study medication and had at least one post-randomization efficacy evaluation. Overall number of participants analyzed are the participants with evaluable data for analyses.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"score on a scale","timeFrame":"Week 8 to Week 14","groups":[{"id":"OG000","title":"Phase C: Aripiprazole/Escitalopram Combination","description":"Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C."},{"id":"OG001","title":"Phase C: Escitalopram Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C."},{"id":"OG002","title":"Phase C: Aripiprazole Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"25"},{"groupId":"OG002","value":"26"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-1.2","spread":"0.4"},{"groupId":"OG001","value":"-1.2","spread":"0.4"},{"groupId":"OG002","value":"-0.2","spread":"0.4"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"=0.995","statisticalMethod":"ANCOVA","paramType":"Treatment Difference","paramValue":"-0.0","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-1.2","ciUpperLimit":"1.2"},{"groupIds":["OG000","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"=0.118","statisticalMethod":"ANCOVA","paramType":"Treatment Difference","paramValue":"-0.9","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-2.1","ciUpperLimit":"0.2"}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"From first dose through 30 days after last dose of study drug (up to approximately 18 weeks)","description":"Phase B Sample- participants who took at least one dose of escitalopram. Phase B+ Sample - participants who responded at end of Phase B (were therefore not randomized) and continued on single-blind escitalopram beyond Week 8. Safety Sample(SS) included those randomized participants in Phase C who received at least one dose of double-blind study medication. 1 participant randomized to escitalopram group, was withdrawn by investigator prior to dosing in Phase C and thus was not included in the SS.","eventGroups":[{"id":"EG000","title":"Phase B: Single-blind Prospective Treatment Phase","description":"Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.","deathsNumAffected":0,"deathsNumAtRisk":211,"seriousNumAffected":2,"seriousNumAtRisk":211,"otherNumAffected":82,"otherNumAtRisk":211},{"id":"EG001","title":"Phase B+: Single-blind Phase B Responders","description":"Participants with response (≥50% reduction in depressive symptom severity in Hamilton Depression Rating Scale {HAM-D17} Total Score; or a HAM-D17 Total Score of \\<14 at Week 8 or a Clinical Global Impression of Improvement {CGI-I} Score of \\<3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B, for up to maximum of Week 14, in Phase B+.","deathsNumAffected":0,"deathsNumAtRisk":45,"seriousNumAffected":0,"seriousNumAtRisk":45,"otherNumAffected":3,"otherNumAtRisk":45},{"id":"EG002","title":"Phase C: Aripiprazole/Escitalopram Combination","description":"Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.","deathsNumAffected":0,"deathsNumAtRisk":28,"seriousNumAffected":0,"seriousNumAtRisk":28,"otherNumAffected":18,"otherNumAtRisk":28},{"id":"EG003","title":"Phase C: Escitalopram Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.","deathsNumAffected":0,"deathsNumAtRisk":27,"seriousNumAffected":1,"seriousNumAtRisk":27,"otherNumAffected":11,"otherNumAtRisk":27},{"id":"EG004","title":"Phase C: Aripiprazole Monotherapy","description":"Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability.","deathsNumAffected":0,"deathsNumAtRisk":28,"seriousNumAffected":1,"seriousNumAtRisk":28,"otherNumAffected":17,"otherNumAtRisk":28}],"seriousEvents":[{"term":"Cholecystitis acute","organSystem":"Hepatobiliary disorders","sourceVocabulary":"MedDra 13.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":211},{"groupId":"EG001","numAffected":0,"numAtRisk":45},{"groupId":"EG002","numAffected":0,"numAtRisk":28},{"groupId":"EG003","numAffected":1,"numAtRisk":27},{"groupId":"EG004","numAffected":0,"numAtRisk":28}]},{"term":"Syncope","organSystem":"Nervous system disorders","sourceVocabulary":"MedDra 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13.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":211},{"groupId":"EG001","numAffected":0,"numAtRisk":45},{"groupId":"EG002","numAffected":0,"numAtRisk":28},{"groupId":"EG003","numAffected":0,"numAtRisk":27},{"groupId":"EG004","numAffected":0,"numAtRisk":28}]},{"term":"Head injury","organSystem":"Injury, poisoning and procedural complications","sourceVocabulary":"MedDra 13.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":211},{"groupId":"EG001","numAffected":0,"numAtRisk":45},{"groupId":"EG002","numAffected":0,"numAtRisk":28},{"groupId":"EG003","numAffected":0,"numAtRisk":27},{"groupId":"EG004","numAffected":0,"numAtRisk":28}]},{"term":"Suicidal ideation","organSystem":"Psychiatric disorders","sourceVocabulary":"MedDra 13.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":211},{"groupId":"EG001","numAffected":0,"numAtRisk":45},{"groupId":"EG002","numAffected":0,"numAtRisk":28},{"groupId":"EG003","numAffected":0,"numAtRisk":27},{"groupId":"EG004","numAffected":0,"numAtRisk":28}]}],"otherEvents":[{"term":"Photophobia","organSystem":"Eye disorders","sourceVocabulary":"MedDRA 13.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":211},{"groupId":"EG001","numAffected":0,"numAtRisk":45},{"groupId":"EG002","numAffected":0,"numAtRisk":28},{"groupId":"EG003","numAffected":0,"numAtRisk":27},{"groupId":"EG004","numAffected":2,"numAtRisk":28}]},{"term":"Vision blurred","organSystem":"Eye disorders","sourceVocabulary":"MedDRA 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