A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states

Authors

Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 11, Issue 8, 904, Article first published online: 16 November 2009

  • This study was funded by Schering-Plough and Pfizer, Inc. All authors significantly contributed to the writing of this manuscript. RSM critically analyzed and interpreted the data. MC, LA, TAM, and JP were involved in the design and execution of the trial. JZ was responsible for the statistical analysis. Editorial support, which consisted of stylistic editing, proofreading, and formatting was provided by Complete Healthcare Communications, Inc., and was funded by Schering-Plough.

  • RSM has received research funding from Wyeth, GlaxoSmithKline, Merck, Servier, and AstraZeneca; and has served as a consultant or speaker for AstraZeneca, Eli Lilly & Co., Janssen-Ortho, Schering-Plough, Wyeth, Lundbeck, GlaxoSmithKline, Oryx, Biovail, Pfizer, Prestwick, and Shire. MC, JZ, and JP are employees of Schering-Plough. LA and TAM were employed at Pfizer Global R&D at the time the study was conducted. The authors have no other commercial associations that might pose a conflict of interest in connection with the manuscript.

Corresponding author:
Roger S. McIntyre, MD, FRCPC
Department of Psychiatry and Pharmacology
University of Toronto
Mood Disorders Psychopharmacology Unit
University Health Network
399 Bathurst Street, MP 9-325
Toronto, Ontario, M5T 2S8, Canada
Fax: 416-603-5368
E-mail: roger.mcintyre@uhn.on.ca

Abstract

Objective:  Asenapine is approved for bipolar disorder and schizophrenia. This was a 3-week, randomized, double-blind, placebo-controlled trial of asenapine for treating acute bipolar mania.

Methods:  After a single-blind placebo run-in period, adults (n = 488) experiencing manic or mixed episodes were randomized to flexible-dose sublingual asenapine (10 mg BID on day 1; 5 or 10 mg BID thereafter; n = 194), placebo (n = 104), or oral olanzapine (15 mg BID on day 1; 5–20 mg QD thereafter; n = 191). Primary efficacy, change in Young Mania Rating Scale (YMRS) total score from baseline to day 21, was assessed using analysis of covariance with last observation carried forward [(LOCF); primary analysis]. A mixed model for repeated measures [(MMRM); prespecified secondary analysis] was also used to assess efficacy. Tolerability and safety assessments included adverse events, physical examinations, extrapyramidal symptom ratings, and laboratory values.

Results:  Mean daily dosages were asenapine 18.2 mg and olanzapine 15.8 mg. Significantly greater least squares (LS) mean ± SE changes in YMRS scores were observed on day 2 with asenapine (−3.0 ± 0.4) and olanzapine (−3.4 ± 0.4) versus placebo (−1.5 ± 0.5, both p < 0.01) and were maintained until day 21 (−10.8 ± 0.8 with asenapine, −12.6 ± 0.8 with olanzapine; both p ≤ 0.0001 versus placebo, −5.5 ± 1.1) with LOCF. The results of MMRM analyses were consistent with those of LOCF. Asenapine had a modest impact on weight and metabolic measures.

Conclusions:  These results indicate that asenapine is rapidly acting, efficacious, and well tolerated for patients with bipolar I disorder experiencing an acute manic episode.

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