Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Participants With Schizophrenia

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of cariprazine at a target dose of 4.5 milligram per day (mg/d) compared with placebo in prevention of relapse in patients with schizophrenia To evaluate the efficacy and safety of cariprazine at a target dose of 3.0 mg/d compared with placebo in prevention of relapse in patients with schizophrenia who were initially stabilized on a target dose of 4.5 mg/d

Official Title
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A Double-Blind, Placebo-Controlled, Randomized Withdrawal, Multicenter Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Cariprazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening). Ability to follow study instructions, complete study assessment tools with minimal assistance and no alteration to the assessment tools, and likely to complete all required visits. Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia as determined by Structured Clinical Interview for DSM-5 (SCID-5). Positive and Negative Syndrome Scale (PANSS) total score >= 70 and <= 120 at Visit 1 and Visit 2 (Day 1). Rating of at least 4 (moderate) on at least 2 of the following 4 PANSS positive symptoms; P1: delusions; P2: conceptual disorganization; P3: hallucinatory behaviour; P6: suspiciousness/persecution at Visit 1 and Visit 2. Exclusion Criteria: Currently meeting DSM-5 criteria for any of the following: Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders Bipolar I and II disorder Autism spectrum disorder, intellectual development disorder, delirium, major/minor neurocognitive disorder History of meeting DSM-5 criteria for substance-related disorders (excluding caffeine-related and tobacco-related disorders) within the prior 3 months before Visit 1. Prior participation in any clinical trials involving experimental or investigational drugs within 6 months before Visit 1 or planned during the study. Female Participants who are pregnant, planning to become pregnant during the course of the study, or are currently lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Cariprazine 4.5 mg/day (Open-label Treatment Period)<br>Cariprazine 1.5 mg capsules orally once daily at Week 1, titrated to 3.0 mg capsules orally once daily at Week 2 and then titrated to 4.5 mg orally once daily from Week 3 through Week 18 in the Open-label Treatment Period. | Drug: Cariprazine<br>* Cariprazine capsules, oral administration, once daily.<br>|
| Placebo Comparator: Placebo (Double-blind Treatment Period)<br>Cariprazine placebo-matching capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period. | Drug: Placebo<br>* Matching placebo capsules, oral administration, once daily.<br>|
| Experimental: Cariprazine 3.0 mg/day (Double-blind Treatment Period)<br>Cariprazine 3.0 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period. | Drug: Cariprazine<br>* Cariprazine capsules, oral administration, once daily.<br>|
| Experimental: Cariprazine 4.5 mg/day (Double-blind Treatment Period)<br>Cariprazine 4.5 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period. | Drug: Cariprazine<br>* Cariprazine capsules, oral administration, once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Relapse During Double-blind Treatment Period | Time to Relapse is the number of days from randomization to first relapse. Relapse is defined as any 1 of the following: Increase in Positive and Negative Syndrome Scale(PANSS) by ≥30% for participants who had total score of ≥50 at randomization or ≥10-point increased score with total score <50 at randomization [PANSS=30 questions where 1=absence of symptoms to 7=extremely severe symptom;total score=30 to 210;higher score more severe symptoms] Increase in Clinical Global Impression-Severity (CGI-S) score by 2 or more points [1=normal to 7=among most extremely ill] Score of >4 on 1 or more of 7 PANSS items:P1-delusions,P2-conceptual disorganization,P3-hallucinatory behavior,P6-suspiciousness,P7-hostility,G8-uncooperativeness,G14-poor impulse control Deliberate self-injury Initiation of treatment with mood stabilizer,antidepressant,antipsychotics or benzodiazepine that exceeds specified allowance Psychiatric hospitalization Exacerbation of psychiatric illness | Randomization (Week 18) to End of Treatment (Week 44) |