A Cariprazine Study in the Prevention of Relapse in Bipolar I Disorder Patients Whose Current Episode is Manic or Depressive, With or Without Mixed Features

Study Overview
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Brief Summary
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1) To evaluate the efficacy and safety of cariprazine at a target dose of 3.0 mg/day compared with placebo in prevention of relapse in patients with bipolar I disorder whose current episode (i.e. index episode) is manic or depressive, with or without mixed features; 2) To evaluate the efficacy and safety of cariprazine at a target dose of 1.5 mg/day compared with placebo in prevention of relapse in patients with bipolar I disorder whose current episode (i.e. index episode) is manic or depressive, with or without mixed features who were initially stabilized on a target dose of 3.0 mg/day

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 Bipolar I Disorder Patients Whose Current Episode is Manic or Depressive, With or Without Mixed Features

Conditions
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Bipolar I Disorder, Mania, Depression

Intervention / Treatment
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* Drug: Cariprazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar I disorder, and at least one of the following two criteria: Current episode manic, with or without mixed features, having a total Young Mania Rating Scale (YMRS) total score ≥ 20 and a score of at least 4 on 2 YMRS items (irritability, speech, content, or disruptive/aggressive behavior); OR current episode depressive, with or without mixed features, having a Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 23 and a score of at least 3 on 2 MADRS items (apparent sadness, reported sadness, inner tension or inability to feel). Exclusion Criteria: Four or more episodes of a mood disturbance within the 12 months before Visit 1; Diagnosis of another psychiatric disorder other than bipolar disorder with the exception of specific phobias.

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: Double-Blind Cariprazine 3.0 mg/day<br>Participants randomized to receive cariprazine 3.0 mg once daily (QD) for up to 39 weeks. | Drug: Cariprazine<br>* Cariprazine capsules, oral administration, once daily<br>|
| Experimental: Double-Blind Cariprazine 1.5 mg/day<br>Participants randomized to receive cariprazine 1.5 mg QD for up to 39 weeks. | Drug: Cariprazine<br>* Cariprazine capsules, oral administration, once daily<br>|
| Placebo Comparator: Double-Blind Placebo<br>Participants randomized to receive placebo QD for up to 39 weeks. | Drug: Placebo<br>* Matching placebo capsules, oral administration, once daily<br>|
| Experimental: Open Label Treatment<br>Participants started on cariprazine 1.5 mg QD, with a target dose of 3.0 mg QD, for up to 16 weeks. | 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 of Any Mood Episode During the Double-Blind Treatment Period | Relapse was defined as the occurrence of any 1 of the following: Young Mania Rating Score (YMRS) total score ≥ 17 (range 0-60; higher score indicates a worse outcome); Montgomery Asberg Depression Rating Scale; (MADRS) total score ≥ 20 (range 0-60; higher score indicates more depressive symptoms); Clinical Global Impression-Improvement scale (CGI-S) ≥ 4 (range from 1 [normal, not at all ill] to 7 [extremely ill]); Initiation of additional psychiatric medication; Psychiatric hospitalization; Exacerbation of illness as judged by clinical impression of the Investigator. Time to first relapse (days) was calculated as the date of the first relapse - the date of randomization + 1. Participants who did not meet the relapse criteria were considered censored at the time of completion or discontinuation from the Double-Blind Treatment Period (DBTP) of the study. Percentiles (95% Confidence Intervals [CI]) are based on Kaplan-Meier estimates. | From Week 16 to Week 55 |