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

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ClinicalTrials.gov Identifier: NCT02054702
Recruitment Status : Completed
First Posted : February 4, 2014
Results First Posted : December 1, 2015
Last Update Posted : December 30, 2015
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

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

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Brexpiprazole Drug: Aripiprazole Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Protocol 331-13-008: An Exploratory, Multicenter, Open-label, Flexible-dose Brexpiprazole (OPC-34712) Trial in Adults With Acute Schizophrenia
Study Start Date : February 2014
Actual Primary Completion Date : June 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: Brexpiprazole
Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally
Drug: Brexpiprazole
Treatment (6 weeks) Up to 4 mg/day, once daily dose, tablets, orally

Experimental: Aripiprazole
Aripiprazole - Up to 20 mg/day, once daily dose, tablets, orally
Drug: Aripiprazole
Up to 20 mg/day, once daily dose, tablets, orally




Primary Outcome Measures :
  1. Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Baseline to Week 6 ]
    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 :
  1. Change From Baseline in Cognitive Test Battery Composite Score [ Time Frame: Baseline to Week 6 ]
    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.

  2. Change From Baseline in Cognitive Test Battery of Early Phase Battery Score [ Time Frame: Baseline to Week 6 ]
    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.

  3. Change From Baseline in Cognitive Test Battery Scores of Groton Maze Learning (GML) [ Time Frame: Baseline to Week 6 ]
    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.

  4. Change From Baseline in Cognitive Test Battery Scores of Detection Task [ Time Frame: Baseline to Week 6 ]
    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.

  5. Change From Baseline in Cognitive Test Battery Scores of Identification Task [ Time Frame: Baseline to Week 6 ]
    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.

  6. Change From Baseline in Cognitive Test Battery Scores of One Card Learning Task [ Time Frame: Baseline to Week 6 ]
    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.

  7. Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score [ Time Frame: Baseline to Week 6 ]
    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.

  8. Mean Change in Clinical Global Impression-Improvement (CGI-I) Score at Week 6 [ Time Frame: Baseline to 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.

  9. Response Rate by Study Week [ Time Frame: Baseline to Week 6 ]
    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).

  10. Change From Baseline to Week 6 in Specific Levels of Functioning Scale (SLOF) Total Score [ Time Frame: Baseline to Week 6 ]
    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.

  11. Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11 Item) Total Score [ Time Frame: Baseline to Week 6 ]
    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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02054702


Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Co., Ltd.
Investigators
Study Director: Junichi Hashimoto, PhD Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02054702     History of Changes
Other Study ID Numbers: 331-13-008
First Posted: February 4, 2014    Key Record Dates
Results First Posted: December 1, 2015
Last Update Posted: December 30, 2015
Last Verified: December 2015

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Schizophrenia
Mental Disorders
Psychotic Disorders
Antipsychotic
Cognitive testing

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Aripiprazole
Brexpiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Agonists
Dopamine Agents