Objective: This phase 3 study evaluated the efficacy, safety, and tolerability of cariprazine in patients with acute exacerbation of schizophrenia. Method: This multinational, randomized, double-blind, placebo-and active-controlled study was conducted from April 2010 to December 2011. Patients who met DSM-IV-TR criteria for schizophrenia were randomized to placebo (n = 153), cariprazine 3 mg/d (n = 155), cariprazine 6 mg/d (n = 157), or aripiprazole 10 mg/d (n = 152) for 6 weeks of double-blind treatment. The primary and secondary efficacy parameters were mean change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness (CGI-S) score, respectively. Results: Least squares mean differences (LSMDs) in PANSS total score change at week 6 significantly favored cariprazine 3 and 6 mg/d versus placebo (LSMD [95% CI]: 3 mg/d, -6.0 [-10.1 to -1.9], adjusted P =.0044; 6 mg/d, -8.8 [-12.9 to -4.7], adjusted P <.0001). Cariprazine 3 and 6 mg/d were also associated with significant improvements relative to placebo in CGI-S scores (LSMD [95% CI]: 3 mg/d, -0.4 [-0.6 to -0.2], adjusted P =.0044; 6 mg/d, -0.5 [-0.7 to -0.3], adjusted P <.0001). Significant differences from placebo were also observed with aripiprazole on the PANSS (LSMD [95% CI]: -7.0 [-11.0 to -2.9], P =.0008) and CGI-S (LSMD [95% CI]: -0.4 [-0.6 to -0.2], P =.0001). Common treatment-emergent adverse events (>= 10%) were insomnia (all groups), akathisia (cariprazine 6 mg/d), and headache (placebo, cariprazine 6 mg/d). Conclusions: This study supports the efficacy, safety, and tolerability of cariprazine 3 and 6 mg/d in the treatment of patients with acute exacerbation of schizophrenia. (C) Copyright 2015 Physicians Postgraduate Press, Inc.
