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).

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, Laurell M, Lieberman JA, Marder SR, Maruff P, McMahon RP, Seidman LJ, Peykamian MA. A phase II study of a histamine H3 receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy.  Schizophrenia Research, 2015; 164(1-3): 136-142.