Cariprazine in Acute Exacerbation of Schizophrenia

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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01104766.