title: Cariprazine in the treatment of acute mania in bipolar I disorder: a double-blind, placebo-controlled, phase III trial.
abstract: BACKGROUND
  This Phase III, randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of flexibly-dosed cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder.
  
  
  METHODS
  Patients were randomized to 3 weeks of double-blind treatment with cariprazine 3-12mg/day (n=158) or placebo (n=154). The primary efficacy parameter was change from baseline to Week 3 in Young Mania Rating Scale (YMRS) total score. The secondary efficacy parameter was change from baseline to Week 3 in Clinical Global Impressions-Severity (CGI-S) score.
  
  
  RESULTS
  Mean change from baseline to Week 3 in YMRS total score was significantly greater for patients receiving cariprazine 3-12mg/day versus placebo (P=0.0004). Significant differences between groups in YMRS total score mean change were observed by Day 4 (first postbaseline assessment) and maintained throughout double-blind treatment (all assessments, P<0.01). Cariprazine also demonstrated statistically significant superiority over placebo on YMRS response (≥50% improvement: cariprazine, 58.9%; placebo, 44.1%; P=0.0097) and remission (YMRS total score≤12: cariprazine, 51.9%; placebo, 34.9%; P=0.0025) and mean change in CGI-S (P=0.0027) score and Positive and Negative Syndrome Scale (PANSS) (P=0.0035) total score. The most common cariprazine-related (≥10% and twice placebo) treatment emergent adverse events (TEAEs) were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting. Mean change from baseline in metabolic parameters were generally small and similar between groups.
  
  
  CONCLUSIONS
  Lack of active comparator arm; short duration of study.
  
  
  CONCLUSIONS
  In this study, cariprazine 3-12mg/day was effective and generally well tolerated in the treatment of manic and mixed episodes associated with bipolar I disorder.
authors.affiliation: Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114-3117, USA. Electronic address: sachsg@aol.com.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Sachs
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Greenberg
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Starace
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lu
authors.affiliation: Prescott Medical Communications Group, Chicago, IL, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Németh
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D017109:Akathisia, Drug-Induced / Q000209:etiology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004415:Dyspepsia / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014202:Tremor / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine
keywords: Antipsychotic; Bipolar disorder; Cariprazine; Dopamine D(3) receptors; Mania; Remission