Efficacy and safety of low- and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study

• Published in: The journal of clinical psychiatry Vol. 76; no. 3; pp. 284 - 292
• Main Authors: Calabrese, Joseph R, Keck, Jr, Paul E, Starace, Anju, Lu, Kaifeng, Ruth, Adam, Laszlovszky, István, Németh, György, Durgam, Suresh
• Format: Journal Article
• Language: English
• Published: United States 01-03-2015
• Subjects: Adolescent; Adult; Aged; Akathisia, Drug-Induced - etiology; Bipolar Disorder - drug therapy; Dopamine Agonists - administration & dosage; Dopamine Agonists - adverse effects; Dopamine Agonists - pharmacology; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - pharmacology; Placebos - administration & dosage; Placebos - adverse effects; Placebos - pharmacology; Remission Induction; Severity of Illness Index; Treatment Outcome; Young Adult
• ISSN: 0160-6689; 1555-2101
• DOI: 10.4088/JCP.14m09081

This phase 3 trial evaluated the efficacy, safety, and tolerability of low- and high-dose cariprazine in patients meeting DSM-IV-TR criteria for acute manic or mixed episodes associated with bipolar I disorder.
This multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed/flexible-dose study was conducted from February 2010 to December 2011. Patients were randomly assigned to placebo, cariprazine 3-6 mg/d, or cariprazine 6-12 mg/d for 3 weeks of double-blind treatment. Primary and secondary efficacy parameters were change from baseline to week 3 in Young Mania Rating Scale (YMRS) total score and Clinical Global Impressions-Severity of Illness (CGI-S) score, respectively. Post hoc analysis examined change from baseline to week 3 in YMRS single items.
A total of 497 patients were randomized; 74% completed the study. The least squares mean difference (LSMD) for change from baseline to week 3 in YMRS total score was statistically significant in favor of both cariprazine groups versus placebo (LSMD [95% CI]: 3-6 mg/d, -6.1 [-8.4 to -3.8]; 6-12 mg/d, -5.9 [-8.2, -3.6]; P < .001 [both]). Both cariprazine treatment groups showed statistically significant superiority to placebo on all 11 YMRS single items (all comparisons, P < .05). Change from baseline in CGI-S scores was statistically significantly greater in both cariprazine groups compared with placebo (LSMD [95% CI]: 3-6 mg/d, -0.6 [-0.9 to -0.4]; 6-12 mg/d, -0.6 [-0.9 to -0.3]; P < .001 [both]). The most common (≥ 5% and twice the rate of placebo) treatment-related adverse events for cariprazine were akathisia (both groups) and nausea, constipation, and tremor (6-12 mg/d only).
Results of this study demonstrated that both low- and high-dose cariprazine were more effective than placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder. Cariprazine was generally well tolerated, although the incidence of akathisia was greater with cariprazine than with placebo.
ClinicalTrials.gov identifier: NCT01058668.