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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054702
• Other study ID #: 331-13-008
• Status: Completed
• Phase: Phase 3
• First received: February 2, 2014
• Last updated: December 1, 2015
• Start date: February 2014
• Est. completion date: July 2014

Study information

• Verified date: December 2015
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: July 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Brexpiprazole
Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally
• Aripiprazole
Up to 20 mg/day, once daily dose, tablets, orally

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Otsuka Pharmaceutical Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No