Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 and Aripiprazole for Treatment of Acute Schizophrenia

Study Overview
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Brief Summary
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This will be a multicenter, randomized, double-blind, placebo-controlled study designed to assess the tolerability, safety, and efficacy of OPC-34712 (0.25 to 6.0 mg) for the treatment of adult subjects hospitalized with an acute relapse of schizophrenia. Aripiprazole (10 to 20 mg) is included as a positive control to confirm the assay sensitivity of the study. A total of approximately 563 subjects will be screened at an estimated 75 sites worldwide in order to obtain approximately 450 randomized subjects.

Official Title
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A Phase 2, 6-Week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 Once Daily and Aripiprazole Once Daily for Treatment of Hospitalized Adult Patients With Acute Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: OPC-34712
* Drug: Placebo
* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 18 and 65 years of age, with a diagnosis of schizophrenia, as defined by DSM-IV-TR criteria Subjects who have been recently hospitalized or who would benefit from hospitalization for an acute relapse of schizophrenia Subjects experiencing an acute exacerbation of psychotic symptoms Exclusion Criteria: Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug Subjects with a current DSM-IV-TR Axis I diagnosis of: Schizoaffective disorder MDD Bipolar disorder Delirium, dementia, amnestic or other cognitive disorder Borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder Subjects presenting with a first episode of schizophrenia Other protocol specific inclusion/exclusion criteria may apply

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>OPC-34712 0.25 mg arm | Drug: OPC-34712<br>* oral, once daily<br>|
| Experimental: 2<br>OPC-34712 low-dose arm | Drug: OPC-34712<br>* oral, once daily<br>|
| Experimental: 3<br>OPC-34712 mid-dose arm | Drug: OPC-34712<br>* oral, once daily<br>|
| Experimental: 4<br>OPC-34712 high-dose arm | Drug: OPC-34712<br>* oral, once daily<br>|
| Placebo Comparator: 5<br> | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: 6<br>Aripiprazole arm | Drug: Aripiprazole<br>* oral, once daily<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 (Double Blind Phase) | The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS total score is 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 ranges from 30-210, with higher scores indicating more severe symptoms. | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms. | Baseline to Week 6 | 
| Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. PANSS negative subscale score is the sum of the rating scores for the 7 negative scale items from the PANSS panel. The PANSS negative subscale score ranges from 7-49, with higher scores indicating more severe symptoms. | Baseline to Week 6 | 
| Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains. The rating is based on four main areas: (a) socially useful activities, including work and study; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The ratings are converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Ratings from 71-100 reflect only mild difficulties. Ratings from 31-70 reflect manifest disabilities of various degrees. Ratings from 1-30 reflect functioning so poor that intensive support or supervision is needed. | Baseline to Week 6 | 
| Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the rater or investigator answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? Response choices include the following: 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; 7=among the most extremely ill patients | Baseline to Week 6 | 
| Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | The rater or investigator rated the particpant's total improvement whether or not it was 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 the following: 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. | Week 6 | 
| Response Rate at Week 6 | Response rate was defined as a reduction of ≥ 30% from baseline in PANSS Total Score; or a CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6 | Week 6 | 
| Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | Efficacy-related discontinuation rate was assessed | Baseline to Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Relapsed