title: Efficacy and Safety of ABT-126 in Subjects with Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Study.
abstract: BACKGROUND
  ABT-126 is a potent, selective α7 nicotinic acetylcholine receptor agonist with putative procognitive effects as a monotherapy in treating Alzheimer's disease (AD).
  
  
  OBJECTIVE
  This randomized, double-blind, placebo-controlled multicenter study (NCT01549834) investigated the efficacy and safety of ABT-126 in subjects with mild-to-moderate AD who were taking stable doses of acetylcholinesterase inhibitors (AChEIs).
  
  
  METHODS
  Subjects received 25 mg ABT-126 (n = 143), 75 mg ABT-126 (n = 145), or placebo (n = 146) once daily for 24 weeks. Subjects who completed the 24-week double-blind study were eligible to enroll in a 28-week open-label extension study (NCT01690195) and received 75 mg ABT-126 daily. The primary efficacy endpoint was the change from baseline to week 24 in the 11-item total score of the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog).
  
  
  RESULTS
  Neither dose of ABT-126 demonstrated significant improvement compared with placebo in the primary efficacy endpoint. However, 25 mg ABT-126 demonstrated significant improvement compared with placebo in ADAS-Cog scores at week 4 (least squares mean difference, -1.21; standard error, 0.51; p <  0.010, one-sided); 75 mg ABT-126 did not demonstrate significant improvements in ADAS-Cog scores compared with placebo at any time point. A treatment effect was not observed for any secondary efficacy measures of cognition, function, or global improvement. ABT-126 was generally well tolerated; the most common adverse events were agitation, constipation, diarrhea, fall, and headache.
  
  
  CONCLUSIONS
  Overall, the efficacy profile of ABT-126 did not warrant further development as add-on therapy to AChEIs to treat mild-to-moderate AD.
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Florian
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meier
authors.affiliation: McGill University Research Center for Studies in Aging, McGill University, Montreal, Quebec, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.affiliation: The Dr. Stanley Lipschitz Clinic, Rosebank, Johannesburg, South Africa.
authors.forename: Stanley
authors.initials: S
authors.lastname: Lipschitz
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.|Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Othman
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gault
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D007391:International Cooperation; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: ABT-126; Acetylcholinesterase inhibitors; alzheimer’s disease; dementia; nicotinic acetylcholine receptors