The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial

Objectives Cariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder. Methods This was a multinational, randomized, double‐blind, placebo‐controlled, flexible‐dose study of cariprazine 3–12 mg/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double‐blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (YMRS) and Clinical Global Impressions–Severity (CGI‐S) scores, respectively. Post‐hoc analysis evaluated changes on YMRS single items. Results In each group, 118 patients received double‐blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8 mg/day. At Week 3, cariprazine significantly reduced YMRS and CGI‐S scores versus placebo, with least square mean differences of −6.1 (p