title: A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.
abstract: BACKGROUND
  ABT-288, a highly selective histamine-3 receptor antagonist, demonstrated efficacy across several preclinical cognitive domains, and safety in healthy subjects and elderly volunteers.
  
  
  OBJECTIVE
  Evaluate the efficacy and safety of ABT-288 in subjects with mild-to-moderate Alzheimer's dementia.
  
  
  METHODS
  The study used a randomized, double-blind, placebo- and active-controlled, parallel group design with pre-defined futility criteria to permit early study termination. A total of 242 subjects were randomized in an equal ratio to ABT-288 1 mg or 3 mg, donepezil 10 mg, or placebo once daily for 12 weeks. The primary efficacy endpoint was the change from baseline to final evaluation on the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score.
  
  
  RESULTS
  The study was prematurely terminated because futility criteria were met. Point estimates on the ADAS-Cog scores for both ABT-288 dose groups were numerically inferior to placebo but no statistical differences were detected. Donepezil demonstrated statistically significant improvement. Adverse events were generally mild and self-limiting.
  
  
  CONCLUSIONS
  ABT-288 did not demonstrate efficacy in the symptomatic treatment of Alzheimer's dementia.
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Haig
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: Yili
authors.initials: Y
authors.lastname: Pritchett
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meier
authors.affiliation: AbbVie, 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, North Chicago, IL, USA.
authors.forename: Coleen
authors.initials: C
authors.lastname: Hall
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gault
authors.affiliation: AbbVie, North Chicago, IL, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lenz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D000704:Analysis of Variance; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D054828:Histamine H3 Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011724:Pyridazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011758:Pyrroles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C576396:2-(4'-(5-methylhexahydropyrrolo(3,4-b)pyrrol-1-yl)biphenyl-4-yl)-2H-pyridazin-3-one; D054828:Histamine H3 Antagonists; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D011724:Pyridazines; D011758:Pyrroles; D000077265:Donepezil
keywords: ABT-288; Alzheimer's dementia; H3 antagonists; cognition; drug therapy; humans