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

L. Fredrik Jarskog; Martin T. Lowy; Richard A. Grove; Richard S.E. Keefe; Joseph P. Horrigan; M. Patricia Ball; Alan Breier; Robert W. Buchanan; Cameron S. Carter; John G. Csernansky; Donald C. Goff; Michael F. Green; Joshua T. Kantrowitz; Matcheri S. Keshavan; Marc Laurelle; Jeffrey A. Lieberman; Stephen R. Marder; Paul Maruff; Robert P. McMahon; Larry J. Seidman; Margaret A. Peykamian

doi:10.1016/j.schres.2015.01.041

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

L. Fredrik Jarskog, Martin T. Lowy, Richard A. Grove, Richard S.E. Keefe, Joseph P. Horrigan, M. Patricia Ball, Alan Breier, Robert W. Buchanan, Cameron S. Carter, John G. Csernansky, Donald C. Goff, Michael F. Green, Joshua T. Kantrowitz, Matcheri S. Keshavan, Marc Laurelle, Jeffrey A. Lieberman, Stephen R. Marder, Paul Maruff, Robert P. McMahon, Larry J. SeidmanMargaret A. Peykamian

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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 7weeks (4weeks 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.

Original language	English
Pages (from-to)	136-142
Number of pages	7
Journal	Schizophrenia Research
Volume	164
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2015.01.041
State	Published - 1 May 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier B.V.

Funding

Research was funded by GlaxoSmithKline . Results submitted in collaboration with the Treatment and Evaluation Network for Trials in Schizophrenia (TENETS) group. The sponsor and authors of this paper would like to thank the patients and investigators who made this research possible, including study investigators Mohommad Bari, Christopher Benbow, Alan Breier, Robert W. Buchanan, Carter S. Cameron, Stephen Glass, Armen Goenjian, Morris Goldman, L. Fredrik Jarskog, Joshua Kantrowitz, Matcheri S. Keshavan, Jeffrey A. Leiberman, Stephen R. Marder, Joseph McEvoy, and Nirav Patel. Grant numbers for author Richard Keefe , NIH # 1R21-MH101685-01A1 , NIH # 1R21-MH101685-02 , Brain Plasticity/NIH : # RC3-MH090833-01 Singapore National Medical Research Council # NMRC/TCR/003/2008 Research Foundation for Mental Hygiene : PO # 96074 .

Funders	Funder number
National Institutes of Health
National Institutes of Health	RC3-MH090833-01, NMRC/TCR/003/2008, 96074
National Institute of Mental Health	R21MH101685
GlaxoSmithKline

Keywords

CogState Schizophrenia Battery
Cognition
GSK239512
Histamine H antagonist
MATRICS Consensus Cognition Battery
Schizophrenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.schres.2015.01.041

Cite this

Jarskog, L. F., Lowy, M. T., Grove, R. A., Keefe, R. S. E., Horrigan, J. P., Ball, M. P., Breier, A., Buchanan, R. W., Carter, C. S., Csernansky, J. G., Goff, D. C., Green, M. F., Kantrowitz, J. T., Keshavan, M. S., Laurelle, M., Lieberman, J. A., Marder, S. R., Maruff, P., McMahon, R. P., ... Peykamian, M. A. (2015). A Phase II study of a histamine H₃ receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy. Schizophrenia Research, 164(1-3), 136-142. https://doi.org/10.1016/j.schres.2015.01.041

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

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 7weeks (4weeks 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 antagonist, MATRICS Consensus Cognition Battery, Schizophrenia",

author = "Jarskog, {L. Fredrik} and Lowy, {Martin T.} and Grove, {Richard A.} and Keefe, {Richard S.E.} and Horrigan, {Joseph P.} and Ball, {M. Patricia} and Alan Breier and Buchanan, {Robert W.} and Carter, {Cameron S.} and Csernansky, {John G.} and Goff, {Donald C.} and Green, {Michael F.} and Kantrowitz, {Joshua T.} and Keshavan, {Matcheri S.} and Marc Laurelle and Lieberman, {Jeffrey A.} and Marder, {Stephen R.} and Paul Maruff and McMahon, {Robert P.} and Seidman, {Larry J.} and Peykamian, {Margaret A.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier B.V.",

year = "2015",

month = may,

day = "1",

doi = "10.1016/j.schres.2015.01.041",

language = "אנגלית",

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Jarskog, LF, Lowy, MT, Grove, RA, Keefe, RSE, Horrigan, JP, Ball, MP, Breier, A, Buchanan, RW, Carter, CS, Csernansky, JG, Goff, DC, Green, MF, Kantrowitz, JT, Keshavan, MS, Laurelle, M, Lieberman, JA, Marder, SR, Maruff, P, McMahon, RP, Seidman, LJ & Peykamian, MA 2015, 'A Phase II study of a histamine H₃ receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy', Schizophrenia Research, vol. 164, no. 1-3, pp. 136-142. https://doi.org/10.1016/j.schres.2015.01.041

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AU - Jarskog, L. Fredrik

AU - Lowy, Martin T.

AU - Grove, Richard A.

AU - Keefe, Richard S.E.

AU - Horrigan, Joseph P.

AU - Ball, M. Patricia

AU - Breier, Alan

AU - Buchanan, Robert W.

AU - Carter, Cameron S.

AU - Csernansky, John G.

AU - Goff, Donald C.

AU - Green, Michael F.

AU - Kantrowitz, Joshua T.

AU - Keshavan, Matcheri S.

AU - Laurelle, Marc

AU - Lieberman, Jeffrey A.

AU - Marder, Stephen R.

AU - Maruff, Paul

AU - McMahon, Robert P.

AU - Seidman, Larry J.

AU - Peykamian, Margaret A.

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N2 - 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 7weeks (4weeks 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.

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