A Phase II study of a histamine H₃ receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy

Schizophr Res. 2015 May;164(1-3):136-42. doi: 10.1016/j.schres.2015.01.041. Epub 2015 Feb 24.

Abstract

This Phase II exploratory study assessed GSK239512, a brain penetrant histamine H₃ receptor antagonist, versus placebo on cognitive impairment in 50 stable outpatients with schizophrenia. Subjects were randomized to placebo or GSK239512 for 7 weeks (4 weeks titration). GSK239512 was associated with a small positive effect size (ES) on the CogState Schizophrenia Battery (CSSB) Composite Score (ES=0.29, CI=-0.40, 0.99) relative to placebo (primary endpoint). GSK239512's ES on CSSB domains were generally positive or neutral except Processing Speed, which favored placebo (ES=-0.46). Effects on the MATRICS Consensus Cognitive Battery were mostly neutral or favored placebo. GSK239512 was generally well tolerated with an adverse event profile consistent with the known class pharmacology. There was no evidence of overall beneficial effects of GSK239512 for CIAS in this population.

Trial registration: ClinicalTrials.gov NCT01009060.

Keywords: CogState Schizophrenia Battery; Cognition; GSK239512; Histamine H(3) antagonist; MATRICS Consensus Cognition Battery; Schizophrenia.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use
  • Benzazepines / therapeutic use*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology*
  • Female
  • Histamine Antagonists / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Schizophrenia / complications*
  • Schizophrenia / drug therapy
  • Treatment Outcome
  • Young Adult

Substances

  • Antipsychotic Agents
  • Benzazepines
  • GSK239512
  • Histamine Antagonists

Associated data

  • ClinicalTrials.gov/NCT01009060