A Study of Cariprazine in the Prevention of Relapse of Symptoms in Participants With Schizophrenia

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy and safety of cariprazine relative to placebo in the prevention of relapse of symptoms in participants with schizophrenia.

Detailed Description
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There were 3 periods (phases) in the study. The Open-label Phase lasted 20 weeks. In the first 6 weeks, participants received 3, 6, or 9 mg cariprazine orally once a day; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this Open-label Phase. At the end of Week 8, participants had to meet the following criteria to continue in the study. Positive and Negative Syndrome Scale (PANSS) total score ≤ 60 at the end of Week 8 At least 20% decrease in PANSS total score from baseline to the end of Week 8 Clinical Global Impressions - Severity (CGI-S) score ≤ 4 at the end of Week 8 Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 8 Stable dose during the previous 2 weeks No significant tolerability issues as judged by the Investigator at the end of Week 8 At the end of the Open-label Phase, participants were randomized into 2 treatment groups, cariprazine or placebo, if they met the following criteria: PANSS total score ≤ 60 at the end of Week 20 At least 20% decrease in PANSS total score from baseline to the end of Week 20 CGI-S score ≤ 4 at the end of Week 20 Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 20 No significant tolerability issues as judged by the Investigator During this Double-blind Treatment Phase, participants received either placebo or cariprazine at the same dosage (3, 6, or 9 mg) that they received during the last 14 weeks of the Open-label Phase. All participants entered the 4 week Safety Follow-up Phase. They received a treatment other than the investigational product at the discretion of the Investigator.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Cariprazine (RGH-188) in the Prevention of Relapse in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Placebo
* Drug: Cariprazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have provided informed consent prior to any study specific procedures. Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR) criteria for schizophrenia. Participants with normal physical examination, laboratory, vital signs, and/or electrocardiogram (ECG). Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening). Positive and Negative Syndrome Scale (PANSS) total score ≥ to 70 and ≤ 120 at Visit 1 (Screening) and Visit 2 (beginning of Run-in Phase). Negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test (applies to female participants of childbearing potential only). Body mass index between 18 and 40 kg/m^2, inclusive. Exclusion Criteria: Participants currently meeting DSM-IV-TR criteria for schizoaffective disorder, schizophreniform disorder, bipolar I and II and known or suspected borderline or antisocial personality disorder. or other DSM-IV-TR axis II disorders. Participants in their first episode of psychosis. Treatment-resistant schizophrenia over the last 2 years. Positive result from the blood alcohol test or from the urine drug screen for any prohibited medication. At imminent risk of injuring self or others or causing significant damage to property. Suicide risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cariprazine - Open-label Phase<br>Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase. | Drug: Cariprazine<br>* Cariprazine was supplied as 1.5 mg capsules (batch numbers BN0009242 and BN00018595) and 3 mg capsules.<br>* Other names: RGH-188;|
| Experimental: Placebo - Double-blind Treatment Phase<br>Participants received placebo orally once a day for 26 to 72 weeks. | Drug: Placebo<br>* Placebo was supplied in capsules.<br>|
| Experimental: Cariprazine - Double-blind Treatment Phase<br>Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks | Drug: Cariprazine<br>* Cariprazine was supplied as 1.5 mg capsules (batch numbers BN0009242 and BN00018595) and 3 mg capsules.<br>* Other names: RGH-188;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Baseline to the First Symptom Relapse During the Double-blind Phase | Relapse was defined as meeting ≥1 of the following criteria:1-Hospitalization due to worsening of condition;2-increase in Positive and Negative Syndrome Scale(PANSS) total score by ≥30% for participants,scored ≥50 or a ≥10-point increase for participants,scored <50 at randomization;3-increase in Clinical Global Impressions-Severity(CGI-S) score by ≥2 points at Week 20;4-deliberate self-injury or aggressive behaviour;5-suicidal/homicidal ideation judged clinically significant by Investigator;6-score of >4 on 1 or more of following PANSS items:P1,P2,P3,P6,P7,G8 or G14. Second assessment not performed based on Investigator discretion. PANSS is 30-item rating scale. Each item scored on 7-point scale. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms. CGI-S is 7-point scale,measures severity of participant's illness in comparison with others with same diagnosis. Lower score indicates less severe illness. 25th percentile for time to relapse was reported. | Up to 34 Weeks and Bi-Weekly thereafter until Week 92 | 

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