A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial

Study Overview
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Brief Summary
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To compare the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy to an assigned open label antidepressant therapy (ADT) in the proposed subject population with MDD.

Detailed Description
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This is a trial designed to assess the safety and efficacy of brexpiprazole (flexible dose) as adjunctive therapy to an assigned known anti-depressant in depressed subjects. The trial consists of a continuous 18-week double-blind treatment period with a 30-day follow-up. Subjects who complete all trial visits through the Week 18 visit may be offered entry into an optional open-label rollover trial.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo and Active Comparator Controlled Trial of Flexible-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial

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

Intervention / Treatment
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* Drug: Brexpiprazole
* Drug: Seroquel XR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent. Subjects with both a diagnosis of MDD, and in a current major depressive episode, as defined by DSM-IV-TR criteria Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period. Exclusion Criteria: Females who are breast-feeding and/or who have a positive pregnancy test result during screening prior to receiving trial medication Subject has a current Axis I (DSM-IV-TR) diagnosis of: dementia, Schizophrenia, Bipolar, Eating disorder , Obsessive-compulsive disorder, Panic disorder, Posttraumatic stress disorder Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current major depressive episode. Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days Subjects currently treated with insulin for diabetes. Subjects with uncontrolled hypertension Subjects with known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass Surgery Subjects with a positive drug screen for cocaine, marijuana, or other illicit drugs Inability to swallow tablets or tolerate oral medication Abnormal laboratory test results, vital signs and ECG results Subjects who previously participated in any prior brexpiprazole clinical trial.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + ADT<br>Matching Placebo and assigned ADT | Drug: Placebo<br>* tablet/capsule<br>|
| Experimental: Brexpiprazole + ADT<br>Brexpiprazole, flexible dose and assigned ADT | Drug: Brexpiprazole<br>* tablet/capsule<br>* Other names: OPC-34712;|
| Active Comparator: Seroquel XR + ADT<br>Seroquel XR, flexible dose and assigned ADT | Drug: Seroquel XR<br>* tablet/capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery Asberg Depression Rating Scale (MADRS) | To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression. | Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sheehan Disability Scale (SDS) | To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment. | Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16). | 
| Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4. | Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression. | Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14) | 
| Clinical Global Impression Score | Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse). | From randomization to Phase B week 6 (14/16 weeks after randomization). | 
| MADRS Response at Week 6 | MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment. | Phase B week 6 (14/16 weeks after randomization). | 
| Number of Participants With MADRS | MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment. | Phase B week 6 (14/16 weeks after randomization). | 
| CGI-I Response Rate | CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment. | Phase B week 6 (14/16 weeks after randomization). | 
| Number of Participants With Adverse Events | To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables. | From screening (Day -28 to Day-1) upto post treatment follow-up. | 
| Sheehan Disability Scale (SDS) Individual Item Scores. | To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe). | Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16). | 

 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