EPA-0870 – Efficacy and Safety of Cariprazine in Patients with Acute Exacerbation of Schizophrenia: Results of two Phase III Trials

Abstract

Introduction:

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

Objective:

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.

Aims:

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

Methods:

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.

Results:

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.

Conclusion:

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