title: Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial.
abstract: OBJECTIVE
  This phase 3 study evaluated the efficacy, safety, and tolerability of cariprazine in patients with acute exacerbation of schizophrenia.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01104766.
authors.affiliation: Clinical Development, Forest Research Institute, an Allergan affiliate, Harborside Financial Center, Plaza V, Jersey City, NJ 07311 suresh.durgam@actavis.com.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lu
authors.forename: Raffaele
authors.initials: R
authors.lastname: Migliore
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.forename: György
authors.initials: G
authors.lastname: Németh
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
mesh_terms: D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068180:Aripiprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D000068180:Aripiprazole; C533287:cariprazine