Efficacy and Safety of the α7-Nicotinic Acetylcholine Receptor Agonist ABT-126 in the Treatment of Cognitive Impairment Associated With Schizophrenia: Results From a Phase 2b Randomized Controlled Study in Smokers.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of the α7-nicotinic receptor agonist ABT-126 for treatment of cognitive impairment in stable subjects with schizophrenia who smoke. METHODS: A 12-week double-blind, placebo-controlled, parallel-group study was conducted from August 2012 to March 2014. Subjects with a diagnosis of schizophrenia based on DSM-IV-TR criteria (confirmed by the Mini-International Neuropsychiatric Interview version 6.0.0) were randomized 111 to ABT-126 25 mg, ABT-126 75 mg, or placebo once daily while maintained on their background antipsychotic medication. The primary endpoint was the change from baseline on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) neurocognitive composite score; the primary analysis compared ABT-126 with placebo at week 12 using a mixed-effects model for repeated measures. Secondary endpoints included the change from baseline on the University of California San Diego Performance-based Skills Assessment-2 Extended-Range, the 16-item Negative Symptom Assessment scale (NSA-16), and safety assessments. RESULTS: Of the 157 randomized subjects, 82% completed the study. The mean baseline MCCB neurocognitive composite score for the entire study sample was 28.8; scores were similar across groups. No statistical difference in the change from baseline score between any of the ABT-126 dose groups and placebo was observed on the MCCB neurocognitive composite score (ABT-126 25 mg, +0.28; ABT-126 75 mg, +0.41; placebo, +1.42). Differences in the NSA-16 total score were seen with ABT-126 75 mg versus placebo at week 6 (-2.79; P = .011) and week 12 (-1.94; P = .053). Adverse events with ABT-126 were similar to placebo, except for constipation (5.8% for ABT-126 vs 0% for placebo). CONCLUSIONS: ABT-126 did not demonstrate a procognitive effect in subjects with stable schizophrenia who smoke. A trend for improvement in negative symptoms was observed with the high dose. The safety profile of ABT-126 was similar to placebo. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT01678755​.