EPA-0869 – Efficacy and safety of cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder

Abstract

Cariprazine is a potent dopamine D 3 and D 2 receptor partial agonist with preferential binding to D 3 receptors. 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. Evaluate the efficacy, safety, and tolerability of cariprazine in mania associated with bipolar I disorder. 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. 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. Cariprazine was effective and generally well tolerated in the treatment of bipolar mania.