Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to explore changes in efficacy, cognitive functioning, and safety of flexibly-dosed Brexpiprazole monotherapy in subjects with acute schizophrenia

Official Title
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Protocol 331-13-008: An Exploratory, Multicenter, Open-label, Flexible-dose Brexpiprazole (OPC-34712) Trial in Adults With Acute Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Brexpiprazole
* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 65 years of age, inclusive, at the time of informed consent with a diagnosis of schizophrenia 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) for Schizophrenia and Psychotic Disorders Studies Would benefit from hospitalization or continued hospitalization for treatment of a current acute relapse of schizophrenia at trial entry Are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by all of the following: Positive and Negative Syndrome Scale (PANSS) Total Score of ≥ 80 Score of ≥ 4 on two or more of the following PANSS items at screening: hallucinatory behavior, unusual thought content, conceptual disorganization, or suspiciousness Clinical Global Impression - Severity of Illness Scale (CGI-S) score ≥ 4 (moderately ill) Exclusion Criteria: Are presenting with a first episode of schizophrenia based on the clinical judgment of the investigator Have been hospitalized > 21 days for the current acute episode at the time of the baseline visit Have a current DSM-IV-TR Axis I diagnosis other than schizophrenia, including, but not limited to, schizoaffective disorder, major depressive disorder (MDD), bipolar disorder, post-traumatic stress disorder, anxiety disorders, delirium, dementia, amnestic, or other cognitive disorders; also borderline, paranoid, histrionic, schizotypal, schizoid, antisocial personality disorders or mental retardation. Improvement of ≥ 20% in total PANSS score between the screening and baseline assessments.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brexpiprazole<br>Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally | Drug: Brexpiprazole<br>* Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally<br>|
| Experimental: Aripiprazole<br>Aripiprazole - Up to 20 mg/day, once daily dose, tablets, orally | Drug: Aripiprazole<br>* Up to 20 mg/day, once daily dose, tablets, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Cognitive Test Battery Composite Score | The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. | Baseline to Week 6 | 
| Change From Baseline in Cognitive Test Battery of Early Phase Battery Score | The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. The cognitive test early phase battery was analyzed; tasks included Groton Maze Learning Task, Detection Task, Identification Task, and One Card Learning Task. | Baseline to Week 6 | 
| Change From Baseline in Cognitive Test Battery Scores of Groton Maze Learning (GML) | The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. | Baseline to Week 6 | 
| Change From Baseline in Cognitive Test Battery Scores of Detection Task | The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. | Baseline to Week 6 | 
| Change From Baseline in Cognitive Test Battery Scores of Identification Task | The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. | Baseline to Week 6 | 
| Change From Baseline in Cognitive Test Battery Scores of One Card Learning Task | The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. | Baseline to Week 6 | 
| Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score | The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this 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. | Baseline to Week 6 | 
| Mean Change in Clinical Global Impression-Improvement (CGI-I) Score at Week 6 | The efficacy of trial medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at Baseline prior to the first dose of double-blind study medication. 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. | Baseline to Week 6 | 
| Response Rate by Study Week | The response rate was defined as reduction of ≥30% from Baseline in PANSS Total Score or CGI-I score of of 1 (very much improved) or 2 (much improved). | Baseline to Week 6 | 
| Change From Baseline to Week 6 in Specific Levels of Functioning Scale (SLOF) Total Score | The SLOF questionnaire used in this trial consisted of 30 items grouped into 4 areas: interpersonal relationships, social acceptability, activities, and work skill. The SLOF correlates with a subject's quality of life. Each of the questions in the domains is rated on a 5-point Likert scale ranging from 1 not well at all to 5 very well. The possible total score range for SLOF is from 30 to 150, higher score indicating better overall functioning of the participant. | Baseline to Week 6 | 
| Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11 Item) Total Score | The BIS-11, a subject-rated scale designed to assess impulsive personality traits, was administered at the baseline and Week 6 visits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, nonplanning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, higher scores indicate better personality trait. | Baseline to Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Mental Disorders, Psychotic Disorders, Antipsychotic, Cognitive testing