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.
L Fredrik Jarskog  1 ,  Martin T Lowy  2 ,  Richard A Grove  3 ,  Richard S E Keefe  4 ,  Joseph P Horrigan  2 ,  M Patricia Ball  5 ,  Alan Breier  6 ,  Robert W Buchanan  5 ,  Cameron S Carter  7 ,  John G Csernansky  8 ,  Donald C Goff  9 ,  Michael F Green  10 ,  Joshua T Kantrowitz  11 ,  Matcheri S Keshavan  12 ,  Marc Laurelle  13 ,  Jeffrey A Lieberman  14 ,  Stephen R Marder  10 ,  Paul Maruff  15 ,  Robert P McMahon  5 ,  Larry J Seidman  12 ,  Margaret A Peykamian  2
Affiliations
  • 1. University of North Carolina School of Medicine, Chapel Hill, NC, United States.
  • 2. GlaxoSmithKline Neurosciences Therapy Area Unit, RTP, NC, United States.
  • 3. GlaxoSmithKline Neurosciences Clinical Statistics, Stockley Park, UK. Electronic address: [email protected].
  • 4. Duke University Medical Center, Durham, NC, United States.
  • 5. Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States.
  • 6. Indiana University School of Medicine, Indianapolis, IN, United States.
  • 7. University of California, Davis, CA, United States.
  • 8. Feinberg School of Medicine, Chicago, IL, United States.
  • 9. Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
  • 10. University of California, Los Angeles, CA, United States.
  • 11. New York State Psychiatric Institute, New York , NY, United States.
  • 12. Harvard Medical School, Boston, MA, United States.
  • 13. GlaxoSmithKline Neuroscience CEDD, Harlow, UK.
  • 14. New York State Psychiatric Institute, New York , NY, United States; Columbia University, New York, NY, United States.
  • 15. Cogstate, Sydney, Australia.
PMID: 25728831 DOI: 10.1016/j.schres.2015.01.041
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.

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