Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial

J Clin Psychiatry. 2015 Dec;76(12):e1574-82. doi: 10.4088/JCP.15m09997.

Abstract

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Aripiprazole / administration & dosage
  • Aripiprazole / adverse effects
  • Aripiprazole / pharmacology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / pharmacology*
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Piperazines
  • Aripiprazole
  • cariprazine

Associated data

  • ClinicalTrials.gov/NCT01104766