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

Summarize data from 2 Phase III, randomized, double-blind (6-week), placebo-controlled trials of fixed-dose cariprazine (3mg/d and 6mg/d, NCT01104766) and flexible-dose cariprazine (3–6mg/d and 6–9mg/d, NCT01104779) in adults with acute exacerbation of schizophrenia.

Evaluate the efficacy, safety, and tolerability of cariprazine in schizophrenia.

Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S), respectively, and were analyzed using a mixed-effects model for repeated measures.

Randomized patient populations: 617 (NCT01104766; 153 placebo, 155 cariprazine 3mg/d, 157 cariprazine 6mg/d, 152 aripiprazole) and 446 (NCT01104779; 147 placebo, 151 cariprazine 3–6mg/d, 148 cariprazine 6–9mg/d). Improvement from baseline to Week 6 on PANSS total scores was significantly greater with cariprazine vs placebo: least square mean difference (LSMD) was −6.0 (3mg/d, P=.0044), −6.8 (3–6mg/d, P=.0029), −8.8 (6mg/d, P<.0001), and −9.9 (6–9mg/d, P<.0001). Cariprazine was significantly superior to placebo on CGI-S: LSMD was −0.4 (3mg/d, P=.0044), −0.3 (3–6mg/d, P=.0115), −0.5 (6mg/d, P<.0001), and −0.5 (6–9mg/d, P=.0002). Aripiprazole (active control, NCT01104766) was superior to placebo on both measures (LSMD: PANSS=−7.0, P=.0008; CGI-S=−0.4, P=.0001). The only common cariprazine-related TEAE (≥5% and twice rate of placebo) that occurred in both studies was akathisia. Changes in metabolic parameters were small and similar to placebo in both studies.

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