title: Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial.
abstract: This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P < 0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P < 0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia.
authors.affiliation: From the *Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY; †Clinical Development, and ‡Statistical Science, Forest Research Institute, Jersey City, NJ; §Prescott Medical Communications Group, Chicago, IL; and ∥Medical Division, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: Stephen
authors.initials: S
authors.lastname: Zukin
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lu
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
authors.forename: Krisztián
authors.initials: K
authors.lastname: Nagy
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
mesh_terms: D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced; D038622:Internationality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011605:Psychoses, Substance-Induced; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine