title: A Randomized Trial to Assess the Efficacy and Safety of ABT-126, a Selective α7 Nicotinic Acetylcholine Receptor Agonist, in the Treatment of Cognitive Impairment in Schizophrenia.
abstract: OBJECTIVE
  The authors sought to evaluate the efficacy and safety of ABT-126, a selective α7 nicotinic receptor partial agonist, in stable patients with schizophrenia.
  
  
  METHODS
  A 12-week, double-blind, placebo-controlled, parallel-group phase 2 study was conducted in 22 centers in the United States. Clinically stable patients with schizophrenia were randomly assigned to receive once-daily dosing with 10 mg of ABT-126, 25 mg of ABT-126, or placebo. The primary efficacy measure was change from baseline to week 12 on the MATRICS Consensus Cognitive Battery (MCCB) composite score compared with placebo, tested by a one-sided t test. Secondary measures included MCCB domain scores and UCSD Performance-Based Skills Assessment total score, each tested by two-sided t tests.
  
  
  RESULTS
  A total of 207 subjects were randomized, of whom 165 (81%) completed the study. ABT-126 showed an improvement that fell short of significance on the MCCB composite score at week 12 (least squares mean difference from placebo, 1.3 and 1.5 for the 10 mg and 25 mg groups, respectively). A significant treatment-by-smoking status interaction was observed on the mean change from baseline to final MCCB composite score: nonsmokers (N=69) demonstrated a difference from placebo of 2.9 (SE=1.4) in the 10 mg group and 5.2 (SE=1.6) in the 25 mg group, whereas no differences were observed in smokers (N=113). Among the nonsmokers in the ABT-126 25 mg group (N=19), significant improvements compared with placebo occurred at final assessment for verbal learning (least squares mean difference=5.5, SE=1.9), working memory (least squares mean difference=5.4, SE=2.0), and attention/vigilance (least squares mean difference=8.7, SE=2.5). The most frequently reported adverse events for ABT-126 were dizziness, diarrhea, and fatigue (all <8% incidence).
  
  
  CONCLUSIONS
  ABT-126 demonstrated a procognitive effect in nonsmoking subjects, particularly in verbal learning, working memory, and attention.
authors.affiliation: From AbbVie, Inc., North Chicago, Ill.; and the Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: George M
authors.initials: GM
authors.lastname: Haig
authors.affiliation: From AbbVie, Inc., North Chicago, Ill.; and the Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Earle E
authors.initials: EE
authors.lastname: Bain
authors.affiliation: From AbbVie, Inc., North Chicago, Ill.; and the Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.affiliation: From AbbVie, Inc., North Chicago, Ill.; and the Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Baker
authors.affiliation: From AbbVie, Inc., North Chicago, Ill.; and the Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Othman
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011594:Psychometrics; D011812:Quinuclidines / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012907:Smoking / Q000009:adverse effects; D013830:Thiadiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014706:Verbal Learning / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: C000618299:ABT-126; D018697:Nootropic Agents; D011812:Quinuclidines; D013830:Thiadiazoles; D064569:alpha7 Nicotinic Acetylcholine Receptor