Single- and multiple-dose pharmacokinetics, safety, and tolerability of the selective alpha7 neuronal nicotinic receptor agonist, ABT-107, in healthy human volunteers.

Author(s): Othman AA, Lenz RA, Zhang J, Li J, Awni WM, Dutta S

Affiliation(s): Department of Clinical Pharmacokinetics and Pharmacodynamics, Abbott Laboratories, 100 Abbott Park Road, Bldg AP13A-3, Abbott Park, IL 60064, USA. ahmed.othman@abbott.com

Publication date & source: 2011-04, J Clin Pharmacol., 51(4):512-26. Epub 2010 May 21.

Publication type: Clinical Trial, Phase I; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

ABT-107 is a potent, selective alpha7 nicotinic receptor agonist under development for treatment of Alzheimer's disease and cognitive deficits associated with schizophrenia. The pharmacokinetics, safety, and tolerability of escalating single oral doses (1, 3, 10, 30, 60, 80, and 100 mg; double-blind, placebo-controlled, randomized, incomplete crossover design) and multiple oral doses (2, 6, and 15 mg once daily for 7 days; double-blind, placebo-controlled, randomized, parallel-group design) of ABT-107 were evaluated. Additionally, effect of food on ABT-107 pharmacokinetics (20-mg single dose) was evaluated using an open-label, 2-period, fasting and nonfasting, randomized, complete crossover design. ABT-107 exhibited nonlinear (more than dose-proportional) pharmacokinetics. ABT-107 half-life ranged from 7 to 10 hours, and steady state was achieved by day 6 of dosing. Food did not have a clinically meaningful effect on ABT-107 exposure. ABT-107 was safe and well tolerated over the tested dose range. The most frequently reported adverse events were nausea, headache, and tremor following single dosing and somnolence following multiple dosing. The pharmacokinetics, safety, and tolerability profiles of ABT-107 pose it as a good candidate for further development.