Asenapine for the treatment of adults with an acute exacerbation of schizophrenia: results from a randomized, double-blind, fixed-dose, placebo-controlled trial with olanzapine as an active control.
Evaluate the efficacy and safety of asenapine 2.5 mg twice daily (bid; n=97) or 5 mg bid (n=113) versus placebo (n=101) in adults with acute exacerbation of schizophrenia.



Adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) schizophrenia diagnosis were randomized to asenapine 2.5 mg bid, 5 mg bid, placebo, or olanzapine 15 mg once daily. The primary objective was to test superiority of asenapine versus placebo as measured by the change from baseline to day 42 in the Positive and Negative Syndrome Scale (PANSS) total score. The key safety objective was to evaluate weight change in asenapine versus olanzapine at day 42.



The primary efficacy endpoint was met; the difference in least squares mean change from baseline to day 42 in PANSS total score between asenapine 5 mg bid and placebo was -5.5 points (unadjusted 95% CI: -10.1, -1.0; multiplicity adjusted P=0.0356). Neither asenapine 2.5 mg bid nor olanzapine 15mg were superior to placebo. Both asenapine groups demonstrated significantly less weight gain than olanzapine at day 42. Significantly higher incidences of oral hypoesthesia and dysgeusia (combined) for asenapine 2.5 mg bid (5.2% vs 0.0%; P=0.0217) and 5 mg bid (7.1% vs 0.0%; P=0.0033) were observed versus placebo. There were no significant differences between asenapine and placebo for insomnia, extrapyramidal symptoms, akathisia, dizziness, or combination of somnolence/sedation/hypersomnia.



This study supports previous efficacy and safety findings of asenapine; asenapine 5 mg bid is the lowest effective dose in adults with schizophrenia. Asenapine was associated with significantly less weight gain than olanzapine at day 42.
1Department of Neuroscience, Merck,Kenilworth, New Jersey,USA.
Ronald
R
Landbloom
1Department of Neuroscience, Merck,Kenilworth, New Jersey,USA.
Mary
M
Mackle
2Department of Statistical Science, Allergan, Jersey City,New Jersey,USA.
Xiao
X
Wu
1Department of Neuroscience, Merck,Kenilworth, New Jersey,USA.
Linda
L
Kelly
1Department of Neuroscience, Merck,Kenilworth, New Jersey,USA.
Linda
L
Snow-Adami
3Department of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario,Canada.
Roger S
RS
McIntyre
5Department of Psychiatry, Forest Research Institute (now Allergan),Jersey City,New Jersey,USA.
Maju
M
Mathews
5Department of Psychiatry, Forest Research Institute (now Allergan),Jersey City,New Jersey,USA.
Carla
C
Hundt
D000328:Adult; D017109:Akathisia, Drug-Induced / Q000209:etiology; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001569:Benzodiazepines / Q000627:therapeutic use*; D003986:Dibenzocycloheptenes; D018450:Disease Progression; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004408:Dysgeusia / Q000139:chemically induced; D005060:Europe; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D006987:Hypesthesia / Q000139:chemically induced; D016018:Least-Squares Analysis; D008297:Male; D009059:Mouth Diseases / Q000139:chemically induced; D000077152:Olanzapine; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D015430:Weight Gain
D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine; D000077152:Olanzapine
Asenapine; efficacy; olanzapine; safety; schizophrenia