Study Stopped
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.
Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
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
2 other identifiers
interventional
137
11 countries
53
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Oct 2010
Shorter than P25 for phase_3
53 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 22, 2010
CompletedFirst Posted
Study publicly available on registry
April 27, 2010
CompletedStudy Start
First participant enrolled
October 4, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2011
CompletedResults Posted
Study results publicly available
December 21, 2021
CompletedDecember 21, 2021
December 1, 2021
11 months
April 22, 2010
November 10, 2021
December 20, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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)
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 (or decrease) from baseline indicates a reduction (or improvement) in symptoms. Last observation carried forward (LOCF) method was used for analyses.
Week 8 to Week 14
Secondary Outcomes (2)
Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at the End of Phase C
Week 14
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)
Week 8 to Week 14
Study Arms (5)
Phase B: Single-blind Prospective Treatment Phase
EXPERIMENTALEscitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the Week 1 (end of Week 1) based upon tolerability profile, for 8 weeks. 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+.
Phase B+: Single-blind Phase B Responders
EXPERIMENTALParticipants with response (≥50% reduction in depressive symptom severity in 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) taken during the final week of Phase B, for an additional 6 weeks (Up to Week 14), in Phase B+.
Phase C: Aripiprazole/Escitalopram Combination
EXPERIMENTALParticipants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
Phase C: Escitalopram Monotherapy
EXPERIMENTALParticipants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
Phase C: Aripiprazole Monotherapy
EXPERIMENTALParticipants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily for 6 weeks (Up to Week 14), in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any visit, based upon tolerability.
Interventions
Escitalopram capsule administered orally, once daily without regard to meals.
Aripiprazole capsule administered orally, once daily without regard to meals.
Eligibility Criteria
You may qualify if:
- Participants with a current diagnosis of a major depressive episode. The current depressive episode must be ≥8 weeks in duration
- Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period
- Participants with a 17-item Hamilton Depression Rating Scale (HAM-D17) Total Score ≥18 at the Baseline for the Prospective Treatment Phase
You may not qualify if:
- Lack of prior treatment with an antidepressant during the current depressive episode
- Participants who report treatment with adjunctive or monotherapy antipsychotic treatment during the current depressive episode.
- Participants experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode
- Participants with epilepsy or significant history of seizure disorders
- Participants with a clinically significant current diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
- Participants who have received electroconvulsive therapy (ECT) in the last 10 years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (53)
Unknown Facility
Tucson, Arizona, 85710, United States
Unknown Facility
Chino, California, 91710, United States
Unknown Facility
Riverside, California, 92506, United States
Unknown Facility
Torrance, California, 90502, United States
Unknown Facility
Hamden, Connecticut, 06518, United States
Unknown Facility
Marietta, Georgia, 30060, United States
Unknown Facility
Belmont, Massachusetts, 02478, United States
Unknown Facility
Weymouth, Massachusetts, 02190, United States
Unknown Facility
Saint Charles, Missouri, 63301, United States
Unknown Facility
St Louis, Missouri, 63141, United States
Unknown Facility
Brooklyn, New York, 11235, United States
Unknown Facility
Garfield Heights, Ohio, 44125, United States
Unknown Facility
Philadelphia, Pennsylvania, 19107, United States
Unknown Facility
East Providence, Rhode Island, 02914, United States
Unknown Facility
Kirkland, Washington, 98033, United States
Unknown Facility
Penticton, British Columbia, V2A 4M4, Canada
Unknown Facility
Vancouver, British Columbia, V6Z 2L4, Canada
Unknown Facility
Burlington, Ontario, L7R 4E2, Canada
Unknown Facility
Osijek, 31000, Croatia
Unknown Facility
Rijeka, 51000, Croatia
Unknown Facility
Zagreb, 10000, Croatia
Unknown Facility
Zagreb, 10090, Croatia
Unknown Facility
Douai, 59500, France
Unknown Facility
Élancourt, 78990, France
Unknown Facility
Baja, 6500, Hungary
Unknown Facility
Balassagyarmat, 2660, Hungary
Unknown Facility
Budapest, 1053, Hungary
Unknown Facility
Budapest, 1137, Hungary
Unknown Facility
Gyula, 5700, Hungary
Unknown Facility
Hyderabad, Andhra Pradesh, 500034, India
Unknown Facility
Visakhapatnam, Andhra Pradesh, 530002, India
Unknown Facility
Mumbai, Maharashtra, 400605, India
Unknown Facility
Tampoi, Johor Bahru, 80100, Malaysia
Unknown Facility
Tampoi, Johor Bahru, 81200, Malaysia
Unknown Facility
Kajang, Selangor, 43000, Malaysia
Unknown Facility
Kuala Lumpur, 50603, Malaysia
Unknown Facility
Bełchatów, 97-400, Poland
Unknown Facility
Bialystok, 15-464, Poland
Unknown Facility
Bialystok, 15-879, Poland
Study Site 1
Choroszcz, 16-070, Poland
Study Site 2
Choroszcz, 16-070, Poland
Unknown Facility
Sosnowiec, 41-200, Poland
Unknown Facility
Tuszyn, 95-080, Poland
Study Site 1
Cape Town, 7530, South Africa
Study Site 2
Cape Town, 7530, South Africa
Unknown Facility
Durban, 3630, South Africa
Unknown Facility
Pretoria, 0001, South Africa
Unknown Facility
Pretoria, 0145, South Africa
Unknown Facility
Pretoria, 0181, South Africa
Unknown Facility
Barcelona, 08003, Spain
Unknown Facility
Salamanca, 37002, Spain
Unknown Facility
Gothenburg, 41685, Sweden
Unknown Facility
Malmo, 21135, Sweden
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
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.
Results Point of Contact
- Title
- Global Clinical Development
- Organization
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 22, 2010
First Posted
April 27, 2010
Study Start
October 4, 2010
Primary Completion
September 1, 2011
Study Completion
September 1, 2011
Last Updated
December 21, 2021
Results First Posted
December 21, 2021
Record last verified: 2021-12
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- 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.
- Access Criteria
- Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.