Abstract:
INTRODUCTION:ABT-288 is a highly potent histamine-3 receptor antagonist that has demonstrated pro-cognitive effects in preclinical models relevant to schizophrenia. This study evaluated the efficacy and safety of two doses of ABT-288 in the treatment of cognitive impairment associated with schizophrenia. METHODS:A randomized, double-blind, placebo-controlled, parallel-group 12-week study was conducted at 23 centers in the United States. Clinically stable subjects with schizophrenia were randomized in an equal ratio to ABT-288 10 mg, ABT-288 25 mg, or placebo once daily while continuing their antipsychotic regimen. The primary efficacy measure was the change from baseline to day 84 evaluation on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) composite score vs placebo. Secondary measures included cognitive functioning and psychiatric scales. Safety assessments and sparse pharmacokinetic sampling were also conducted. RESULTS:A total of 214 subjects were randomized. The mean baseline MCCB composite score was 28.4. Approximately 80% of subjects completed the study. The MCCB composite score mean change from baseline to day 84 was numerically worse for both the 10 mg (1.90, P = .618) and 25 mg (0.64, P = .946) doses of ABT-288 vs placebo (2.19). Results from the secondary measures were consistent with the primary analysis. Subjects' schizophrenia symptoms remained stable throughout the study as evidenced by stable Positive and Negative Syndrome Scale scores. Overall, study medication was tolerated; however, an increased incidence of psychosis-related and sleep-related adverse events was associated with ABT-288. DISCUSSION:Neither dose of ABT-288 resulted in cognitive improvement in clinically stable adults with schizophrenia.
journal_name
Schizophr Bulljournal_title
Schizophrenia bulletinauthors
Haig GM,Bain E,Robieson W,Othman AA,Baker J,Lenz RAdoi
10.1093/schbul/sbt240subject
Has Abstractpub_date
2014-11-01 00:00:00pages
1433-42issue
6eissn
0586-7614issn
1745-1701pii
sbt240journal_volume
40pub_type
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