Back to resultsBrexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Brexpiprazole
Aripiprazole
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Mental Disorders, Psychotic Disorders, Antipsychotic, Cognitive testing
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Brexpiprazole
Aripiprazole
Arm Description
Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally
Aripiprazole - Up to 20 mg/day, once daily dose, tablets, orally
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
Full Information
NCT ID
NCT02054702
First Posted
February 2, 2014
Last Updated
December 1, 2015
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
Otsuka Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02054702
Brief Title
Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia
Official Title
Protocol 331-13-008: An Exploratory, Multicenter, Open-label, Flexible-dose Brexpiprazole (OPC-34712) Trial in Adults With Acute Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
Otsuka Pharmaceutical Co., Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Mental Disorders, Psychotic Disorders, Antipsychotic, Cognitive testing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brexpiprazole
Arm Type
Experimental
Arm Description
Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally
Arm Title
Aripiprazole
Arm Type
Experimental
Arm Description
Aripiprazole - Up to 20 mg/day, once daily dose, tablets, orally
Intervention Type
Drug
Intervention Name(s)
Brexpiprazole
Intervention Description
Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Intervention Description
Up to 20 mg/day, once daily dose, tablets, orally
Primary Outcome Measure Information:
Title
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
Description
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).
Time Frame
Baseline to Week 6
Secondary Outcome Measure Information:
Title
Change From Baseline in Cognitive Test Battery Composite Score
Description
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.
Time Frame
Baseline to Week 6
Title
Change From Baseline in Cognitive Test Battery of Early Phase Battery Score
Description
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.
Time Frame
Baseline to Week 6
Title
Change From Baseline in Cognitive Test Battery Scores of Groton Maze Learning (GML)
Description
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.
Time Frame
Baseline to Week 6
Title
Change From Baseline in Cognitive Test Battery Scores of Detection Task
Description
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.
Time Frame
Baseline to Week 6
Title
Change From Baseline in Cognitive Test Battery Scores of Identification Task
Description
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.
Time Frame
Baseline to Week 6
Title
Change From Baseline in Cognitive Test Battery Scores of One Card Learning Task
Description
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.
Time Frame
Baseline to Week 6
Title
Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score
Description
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.
Time Frame
Baseline to Week 6
Title
Mean Change in Clinical Global Impression-Improvement (CGI-I) Score at Week 6
Description
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.
Time Frame
Baseline to Week 6
Title
Response Rate by Study Week
Description
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).
Time Frame
Baseline to Week 6
Title
Change From Baseline to Week 6 in Specific Levels of Functioning Scale (SLOF) Total Score
Description
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.
Time Frame
Baseline to Week 6
Title
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11 Item) Total Score
Description
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.
Time Frame
Baseline to Week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junichi Hashimoto, PhD
Organizational Affiliation
Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia
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