title: Cariprazine in the treatment of schizophrenia: a proof-of-concept trial.
abstract: This 6-week, double-blind, placebo-controlled, proof-of-concept study evaluated the efficacy, safety, and tolerability of low-dose (1.5-4.5 mg/day) and high-dose (6-12 mg/day) cariprazine in patients with acute exacerbation of schizophrenia (NCT00404573). The primary efficacy measure was change in the Positive and Negative Syndrome Scale (PANSS) total score, analyzed using a last observation carried forward approach. Other efficacy measures included the Clinical Global Impression-Severity (secondary) and PANSS subscales (additional). There were no significant differences between the two doses of cariprazine and placebo in PANSS total score change or any other efficacy parameter after multiplicity adjustment. However, low-dose cariprazine versus placebo showed significantly greater reductions in PANSS total (P=0.033) and PANSS negative (P=0.027) scores without multiplicity adjustment. Common treatment-emergent adverse events (incidence≥5% and twice that in the placebo group in either cariprazine dose group) were akathisia, restlessness, tremor, back pain, and extrapyramidal disorder. In this study, the overall cariprazine treatment effect was not statistically significant, but patients treated with low-dose cariprazine showed significantly greater improvement in schizophrenia symptoms relative to placebo-treated patients. Cariprazine was generally well tolerated. Results of this study suggest that cariprazine may be effective in treating schizophrenia and future research is warranted.
authors.affiliation: Departments of aClinical Development bBiostatistics, Forest Research Institute (an Allergan affiliate), Harborside Financial Center, Jersey City, New Jersey cCBH Health LLC, Rockville, Maryland, USA dMedical Division, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.forename: Robert E
authors.initials: RE
authors.lastname: Litman
authors.forename: Kelly
authors.initials: K
authors.lastname: Papadakis
authors.forename: Dayong
authors.initials: D
authors.lastname: Li
authors.forename: György
authors.initials: G
authors.lastname: Németh
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine