Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to explore the effects of fixed-dosed brexpiprazole adjunctive treatment in subjects with Major Depressive Disorder with irritability

Official Title
-----------------
Protocol 331-13-004: An Exploratory, Multicenter, Single-blind, fMRI Study of Fixed-dose Brexpiprazole (OPC 34712) (2 mg/Day Tablets) as an Adjunctive Treatment

Conditions
-----------------
Major Depressive Disorder and Irritability

Intervention / Treatment
-----------------
* Drug: Brexpiprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Are 18 to 55 years of age, inclusive, at the time of informed consent with a diagnosis of a single or recurrent, nonpsychotic episode of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR™) and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) and an adequate clinical psychiatric evaluation Have received a single, trial-approved SSRI or SNRI at an adequate dose for ≥ 6 weeks prior to screening Have a treatment history of inadequate ADT response to at least one ADT (but not > 3) for the current episode. The current major depressive episode must be ≥ 6 weeks in duration. (An inadequate ADT response is defined as < 50% reduction in depressive symptom severity, as measured by subject self-report on the MGH-ATRQ.) To be eligible for this trial Have a MADRS Total Score of 20 or more at screening and the Phase A baseline, and have a MADRS Total Score of 18 or more at the Phase B baseline Have no more than 20% improvement in MADRS Total Score at Phase B baseline compared to Phase A baseline Have a score of 6 or more on the KSQ based on the Well being and Reversal Distress Anger-hostility subscales at screening, Phase A baseline, and Phase B baseline Have anger attacks as documented by the AAQ at screening, Phase A baseline, and Phase B baseline Are right-handed (defined according to the Edinburgh Handedness Inventory) and have normal hearing and normal/corrected-to-normal vision Are willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period Eligibility confirmed through a telephone SAFER interview with the subject and an independent expert centralized rater Exclusion Criteria: Have a current need for involuntary commitment or have been hospitalized within 4 weeks of screening for the current major depressive episode Have a current DSM-IV-TR Axis I diagnosis of any of the following: delirium, dementia, amnestic, or other cognitive disorders; schizophrenia, schizoaffective disorder, or other psychotic disorders; bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified; eating disorders (including anorexia nervosa or bulimia); obsessive compulsive disorder; panic disorder; or post-traumatic stress disorder Have any of the following current Axis II DSM-IV-TR diagnoses: borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorders, or mental retardation Experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brexpiprazole<br>Brexpiprazole - Up to 2 mg/day, once daily dose, tablets, orally | Drug: Brexpiprazole<br>* Treatment (6 weeks) Up to 2 mg/day, once daily dose, tablets, orally<br>* Other names: OPC-34712;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Phase B baseline to Phase B Week 6 in functional magnetic resonance imaging (fMRI) BOLD activation score in the ventromedial prefrontal cortex and amygdala, scanned by fMRI during performance of the Emotion-induction Task |  | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Phase B baseline to Phase B Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Spielberger State Trait Anger Expression Inventory (STAXI-2) Part 1 |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Visual Analog Scale (VAS) |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) score |  | Week 6 | 
| Clinical Global Impression - Improvement Scale (CGI-I) score at Phase B Week 6 |  | Week 6 | 
| MADRS response rate, where response is defined as ≥ 50% reduction in respective total scores from Phase B baseline to Phase B Week 6 |  | Week 6 | 
| MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Phase B baseline to Phase B Week 6 |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Sheehan Disability Scale (SDS) 3-item mean score |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Anger Attacks Questionnaire (AAQ) score |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Symptoms of Depression Questionnaire (SDQ) |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Kellner Symptom Questionnaire (KSQ) |  | Week 6 | 
| Change from Phase B baseline to Phase B Week 6 in Barratt Impulsiveness Scale 11 item (BIS-11) Total Score |  | Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major Depressive Disorder, Mental Disorders, nonpsychotic episode, antipsychotic, Mood Disorder, psychotic disorder