The α7 Nicotinic Agonist ABT-126 in the Treatment of Cognitive Impairment Associated with Schizophrenia in Nonsmokers: Results from a Randomized Controlled Phase 2b Study.
A double-blind, placebo-controlled, parallel-group, 24-week, multicenter trial was conducted to evaluate the efficacy and safety of 3 doses of ABT-126, an α7 nicotinic receptor agonist, for the treatment of cognitive impairment in nonsmoking subjects with schizophrenia. Clinically stable subjects were randomized in 2 stages: placebo, ABT-126 25 mg, 50 mg or 75 mg once daily (stage 1) and placebo or ABT-126 50 mg (stage 2). The primary analysis was the change from baseline to week 12 on the MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score for ABT-126 50 mg vs placebo using a mixed-model for repeated-measures. A key secondary measure was the University of California Performance-based Assessment-Extended Range (UPSA-2ER). A total of 432 subjects were randomized and 80% (344/431) completed the study. No statistically significant differences were observed in either the change from baseline for the MCCB neurocognitive composite score (+2.66 [±0.54] for ABT-126 50 mg vs +2.46 [±0.56] for placebo at week 12; P>0.05) or the UPSA-2ER. A trend for improvement was seen at week 24 on the 16-item Negative Symptom Assessment Scale total score for ABT-126 50 mg (change from baseline -4.27±[0.58] vs -3.00±[0.60] for placebo; P=0.059). Other secondary analyses were generally consistent with the primary end point results. Adverse event rates were similar for ABT-126 and placebo. ABT-126 did not demonstrate a consistent effect on cognition in nonsmoking subjects with schizophrenia; however, a trend toward an effect was observed on negative symptoms. ClincalTrials.gov registration: NCT01655680.
Abbvie Inc., North Chicago, IL, USA.
George
G
Haig
Abbvie Inc., North Chicago, IL, USA.
Deli
D
Wang
Abbvie Inc., North Chicago, IL, USA.|Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Ahmed A
AA
Othman
Abbvie Inc., North Chicago, IL, USA.
Jun
J
Zhao
D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009483:Neuropsychological Tests; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology; D013830:Thiadiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
C000618299:ABT-126; D018722:Nicotinic Agonists; D011812:Quinuclidines; D013830:Thiadiazoles