EPA-0869 – Efficacy and Safety of Cariprazine in Patients with Acute Manic or Mixed Episodes Associated with Bipolar I Disorder

Abstract

Introduction:

Cariprazine is a potent dopamine D₃ and D₂ receptor partial agonist with preferential binding to D₃ receptors.

Objective:

Summarize data from two Phase III, randomized, double-blind, placebo-controlled, flexible-dose, 3-week trials of cariprazine 3-12mg/d (NCT01058096) and cariprazine 3-6mg/d or 6-12mg/d (NCT01058668) in adults with bipolar I disorder and acute manic or mixed episodes.

Aims:

Evaluate the efficacy, safety, and tolerability of cariprazine in mania associated with bipolar I disorder.

Methods:

Primary and secondary efficacy parameters were change from baseline to Week 3 on the Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S), respectively, and were analyzed using a mixed-effects model for repeated measures.

Results:

Randomized patient populations: 312 (NCT01058096; 154 placebo, 158 cariprazine 3–12mg/d) and 497 (NCT01058668; 161 placebo, 167 cariprazine 3–6mg/d, 169 cariprazine 6–12mg/d). Improvement from baseline to Week 3 on YMRS was significantly greater for each cariprazine group vs placebo (P<0.001): least square mean difference (LSMD) was −4.3 (3–12mg/d), −6.1 (3–6mg/d) and −5.9 (6–12mg/d). For each cariprazine group, significantly more patients met YMRS response and remission criteria vs placebo. Cariprazine also was significantly superior to placebo on the CGI-S: LSMD was −0.4 (3–12mg/d, P=.0027), −0.6 (3–6mg/d, P<.001), −0.6 (6–12mg/d, P<.001). The only common cariprazine-related TEAEs (≥5% and twice rate of placebo) that occurred in both studies were akathisia and tremor. Changes in metabolic parameters were small and similar to placebo in both studies.

Conclusions:

Cariprazine was effective and generally well tolerated in the treatment of bipolar mania.