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

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

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.

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.

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.