title: An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial.
abstract: BACKGROUND
  Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.
  
  
  METHODS
  This study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5mg/d, cariprazine 3.0mg/d, cariprazine 4.5mg/d, or risperidone 4.0mg/d (for assay sensitivity) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales.
  
  
  RESULTS
  Of 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5mg/d, 3.0mg/d, and 4.5mg/d (least squares mean difference [LSMD]: -7.6, -8.8, -10.4, respectively; p<0.001; LOCF) and risperidone (-15.1, p<0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p<0.05). The most frequent cariprazine AEs (≥ 5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups.
  
  
  CONCLUSIONS
  The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.
authors.affiliation: Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: suresh.durgam@frx.com.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.affiliation: Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: anju.starace@frx.com.
authors.forename: Anju
authors.initials: A
authors.lastname: Starace
authors.affiliation: Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: dayong.li@frx.com.
authors.forename: Dayong
authors.initials: D
authors.lastname: Li
authors.affiliation: Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: raffaele.migliore@frx.com.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Migliore
authors.affiliation: Prescott Medical Communications Group, 205 N. Michigan Ave, Suite 3400, Chicago, IL, USA. Electronic address: aruth@prescottmed.com.
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
authors.affiliation: Gedeon Richter Plc, H-1103 Budapest 10, Gyomroi u. 19-21, Hungary. Electronic address: gy.nemeth@richter.hu.
authors.forename: György
authors.initials: G
authors.lastname: Németh
authors.affiliation: Gedeon Richter Plc, H-1103 Budapest 10, Gyomroi u. 19-21, Hungary. Electronic address: i.laszlovszky@richter.hu.
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine
keywords: Antipsychotic; Cariprazine; D(3); Dopamine; Schizophrenia