Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adults With Major Depressive Disorder (the Orion Trial)

Study Overview
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Brief Summary
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To assess the long-term safety and tolerability of oral OPC-34712 (brexpiprazole), given in addition to an FDA approved antidepressant (ADT) for the treatment of adults with Major Depressive Disorder (MDD)

Official Title
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A Long-term, Phase 3, Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adults With Major Depressive Disorder, the Orion Trial

Conditions
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Depressive Disorder, Depression, Depressive Disorder, Major, Mood Disorders, Mental Disorders

Intervention / Treatment
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* Drug: OPC-34712
* Drug: Escitalopram
* Drug: Fluoxetine
* Drug: Paroxetine CR
* Drug: Sertraline
* Drug: Duloxetine
* Drug: Venlafaxine XR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female outpatients 18-65 years of age Eligible subjects from Trials 331-10-227, 331-10-228 or 331-12-282: Subjects who completed participation in the Double-blind Randomization Phase (i.e. Week 14 visit) in Trial 331-10-227, Trial 331-10-228, or Trial 331-12-282 or Subjects who met criteria for a response, but did not meet criteria for remission at Week 14 of either trial Eligible subjects from other Phase 3, Double-blind, Brexpiprazole MDD trials: • Subjects who completed the last scheduled visit of the prior Double-blind Randomized Phase 3 trial. Exclusion Criteria: Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving OPC-34712. Subjects with a major protocol violation during the course of their participation in the Double-blind Randomization Phase

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPC-34712 (Brexpiprazole) and Escitalopram<br>OPC-34712: Oral tablet; 0.5 to 3 mg/day Escitalopram: Oral tablet; 10 or 20 mg/day | Drug: OPC-34712<br>* Tablet<br>Drug: Escitalopram<br>* Tablet<br>* Other names: Lexapro;|
| Experimental: OPC-34712 and Fluoxetine<br>OPC-34712: Oral tablet; 0.5 to 3 mg/day Fluoxetine: Oral capsules; 20 or 40 mg/day | Drug: OPC-34712<br>* Tablet<br>Drug: Fluoxetine<br>* Capsule<br>* Other names: Prozac;|
| Experimental: OPC-34712 and Paroxetine CR<br>OPC-34712: Oral tablet; 0.5 to 3 mg/day Paroxetine CR: Oral controlled-release tablets; 37.5 or 50 mg/day | Drug: OPC-34712<br>* Tablet<br>Drug: Paroxetine CR<br>* Controlled-release tablets<br>* Other names: Paxil CR;|
| Experimental: OPC-34712 and Sertraline<br>OPC-34712: Oral tablet; 0.5 to 3 mg/day Sertraline: Oral tablets; 100, 150, or 200 mg/day | Drug: OPC-34712<br>* Tablet<br>Drug: Sertraline<br>* Tablets<br>* Other names: Zoloft;|
| Experimental: OPC-34712 and Duloxetine<br>OPC-34712: Oral tablet; 0.5 to 3 mg/day Duloxetine: Oral delayed-release capsules; 40 or 60 mg/day | Drug: OPC-34712<br>* Tablet<br>Drug: Duloxetine<br>* Delayed-release capsules<br>* Other names: Cymbalta;|
| Experimental: OPC-34712 and Venlafaxine XR<br>OPC-34712: Oral tablet; 0.5 to 3 mg/day Venlafaxine XR: Oral extended-release capsules; 75, 150, or 225 mg/day | Drug: OPC-34712<br>* Tablet<br>Drug: Venlafaxine XR<br>* Extended-release capsules<br>* Other names: Effexor XR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) - All Participants | To assess the frequency and severity of AEs as the variables of safety and tolerability of brexpiprazole. | From screening to week 52/early termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) of Illness Score | The severity of illness for each participant was rated using the CGI-S . On the basis of the investigator answer to the question: Considering your total clinical experience with this particular population, how mentally ill was the participant at that time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. | From screening to week 52/early termination | 
| Change From Baseline in Mean Clinical Global Impression - Improvement (CGI-I) Score | The efficacy of trial treatment was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at screening. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse and 7 = very much worse. | From screening to week 52/early termination | 
| Summary of Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score | The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on regular life responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains with scores from 0 = not at all, to 10 = extremely. Scores of 5 and above were associated with significant functional impairment. | From screening to week 52/early termination | 
| Change From Baseline in the Inventory of Depressive Symptomatology - Self Report (IDS-SR) Total Score | The IDS-SR was a 30-item self-report measure used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of MDD. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. The IDS-SR Total Score is the sum of ratings of 28 item scores. The possible IDS-SR Total Score ranges from 0 (best) to 84 (worst). Under item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. If the number of items recorded is at least 23 and at most 27, the IDS-SR Total Score will be the mean of the recorded items multiplied by 28 and then rounded to the first decimal place. | From screening to week 52/early termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OPC-34712, brexpiprazole, Major Depressive Disorder, Adjunctive Treatment