title: Safety and Efficacy from an 8 Week Double-Blind Trial and a 26 Week Open-Label Extension of Asenapine in Adolescents with Schizophrenia.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the safety and efficacy of asenapine in adolescents with schizophrenia.
  
  
  METHODS
  In an 8 week, randomized, double-blind placebo-controlled trial, subjects (12-17 years of age) meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria for schizophrenia were randomized 1:1:1 to placebo, asenapine 2.5 mg b.i.d., or asenapine 5 mg b.i.d. Subjects who completed the 8 week acute study could participate in a 26 week flexible-dose asenapine-only open-label extension (OLE).
  
  
  RESULTS
  A similar percentage of subjects completed treatment on day 56 (2.5 mg b.i.d. (n=98): 83%; 5 mg b.i.d. [n=106]: 79%; placebo [n=102]: 79%). In the mixed model for repeated measures analysis of the primary end-point (with Hochberg correction for multiplicity), least squares (LS) mean differences between asenapine and placebo on the Positive and Negative Syndrome Scale (PANSS) total score at day 56 were not significant (-4.8 for 2.5 mg b.i.d., p=0.070; -5.6 for 5 mg b.i.d., p=0.064). Significant improvement in the Clinical Global Impressions-Severity score was observed in the 5 mg b.i.d. group versus placebo on day 56 (LS mean -0.3, p=0.024). In the acute phase, ≥7% weight gain and the composite event of somnolence, sedation, and hypersomnia were more common in both asenapine groups than in the placebo group. Akathisia, fasting glucose elevation, and extrapyramidal syndrome were more common in the 5 mg b.i.d. group than in the placebo group. There were no unexpected adverse events in the OLE, and PANSS total scores decreased by -16.1 points in the group previously treated with placebo (n=62) and by -11.2 points in the continuous asenapine group (n=131) from OLE baseline to week 26.
  
  
  CONCLUSIONS
  Although improvements in PANSS total score at day 56 of the acute phase were numerically greater for both asenapine 2.5 and 5 mg b.i.d. than for placebo and were maintained in the OLE, the primary end-point did not achieve statistical significance in the acute phase. No new or unexpected safety concerns were detected during the acute phase or after an additional 26 weeks of asenapine treatment in the adolescent population with schizophrenia.
  
  
  BACKGROUND
  NCT01190254 and NCT1190267 at ClinicalTrials.gov.
authors.affiliation: 1 The Johns Hopkins University/Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: 2 Merck , Whitehouse Station, New Jersey.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Landbloom
authors.affiliation: 2 Merck , Whitehouse Station, New Jersey.
authors.forename: Mary
authors.initials: M
authors.lastname: Mackle
authors.affiliation: 3 Merck , Whitehouse Station, New Jersey.
authors.forename: Wendi
authors.initials: W
authors.lastname: Pallozzi
authors.affiliation: 4 Merck , Oss, The Netherlands .
authors.forename: Sabine
authors.initials: S
authors.lastname: Braat
authors.affiliation: 5 Forest Research Institute , an affiliate of Actavis Inc, Jersey City, New Jersey.
authors.forename: Carla
authors.initials: C
authors.lastname: Hundt
authors.affiliation: 6 University of Colorado/Children's Hospital Colorado , Aurora, Colorado.
authors.forename: Marianne Z
authors.initials: MZ
authors.lastname: Wamboldt
authors.affiliation: 5 Forest Research Institute , an affiliate of Actavis Inc, Jersey City, New Jersey.
authors.forename: Maju
authors.initials: M
authors.lastname: Mathews
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; C522667:asenapine