A Phase II study of a histamine H₃ receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy.
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.
University of North Carolina School of Medicine, Chapel Hill, NC, United States.
L Fredrik
LF
Jarskog
GlaxoSmithKline Neurosciences Therapy Area Unit, RTP, NC, United States.
Martin T
MT
Lowy
GlaxoSmithKline Neurosciences Clinical Statistics, Stockley Park, UK. Electronic address: Richard.a.grove@gsk.com.
Richard A
RA
Grove
Duke University Medical Center, Durham, NC, United States.
Richard S E
RS
Keefe
GlaxoSmithKline Neurosciences Therapy Area Unit, RTP, NC, United States.
Joseph P
JP
Horrigan
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States.
M Patricia
MP
Ball
Indiana University School of Medicine, Indianapolis, IN, United States.
Alan
A
Breier
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States.
Robert W
RW
Buchanan
University of California, Davis, CA, United States.
Cameron S
CS
Carter
Feinberg School of Medicine, Chicago, IL, United States.
John G
JG
Csernansky
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
Donald C
DC
Goff
University of California, Los Angeles, CA, United States.
Michael F
MF
Green
New York State Psychiatric Institute, New York , NY, United States.
Joshua T
JT
Kantrowitz
Harvard Medical School, Boston, MA, United States.
Matcheri S
MS
Keshavan
GlaxoSmithKline Neuroscience CEDD, Harlow, UK.
Marc
M
Laurelle
New York State Psychiatric Institute, New York , NY, United States; Columbia University, New York, NY, United States.
Jeffrey A
JA
Lieberman
University of California, Los Angeles, CA, United States.
Stephen R
SR
Marder
Cogstate, Sydney, Australia.
Paul
P
Maruff
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States.
Robert P
RP
McMahon
Harvard Medical School, Boston, MA, United States.
Larry J
LJ
Seidman
GlaxoSmithKline Neurosciences Therapy Area Unit, RTP, NC, United States.
Margaret A
MA
Peykamian
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D005260:Female; D006633:Histamine Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy; D016896:Treatment Outcome; D055815:Young Adult
D014150:Antipsychotic Agents; D001552:Benzazepines; C584220:GSK239512; D006633:Histamine Antagonists
CogState Schizophrenia Battery; Cognition; GSK239512; Histamine H(3) antagonist; MATRICS Consensus Cognition Battery; Schizophrenia