Evaluation of Cognitive Function in Healthy Older Subjects Treated with Fesoterodine

Abstract

Objective: To evaluate the cognitive effects of fesoterodine 4 and 8 mg versus placebo in healthy older adults. Methods: This was an active– and placebo–controlled, double–blind, double–dummy crossover study conducted using healthy volunteers (aged 65–85 years) with baseline Mini–Mental State Examination score ≥ 26. The study comprised 4 treatment periods: fesoterodine 4 mg for 6 days; fesoterodine 4 mg for 3 days followed by fesoterodine 8 mg for 3 days; placebo for 6 days; and placebo for 6 days with alprazolam 1 mg on day 6. The treatment sequence was randomized, with a 3– to 6–day washout between periods. Subjects completed computer–based cognitive assessments and the Rey Auditory Verbal Learning Test on day 1 (before dosing) and day 6 (after dosing) of each period. The primary endpoint was the Detection task; secondary endpoints were the Identification task, 1–card learning task, Continuous Paired Associate Learning task, Groton Maze Learning Task, and the Rey Auditory Verbal Learning Test. Results: Among 18 subjects in the per protocol set, changes from baseline to day 6 with fesoterodine 4 and 8 mg were not significantly different from placebo for any endpoint (P < 0.05); alprazolam produced significant impairment in all endpoints versus placebo (P < 0.05). No serious adverse events were reported; the most common adverse events were dry mouth for fesoterodine and sedation for alprazolam. No sedation was reported with fesoterodine. Conclusion: In healthy older adults, fesoterodine 4 and 8 mg once daily had no statistically significant effects versus placebo on any cognitive function assessed, including memory; alprazolam 1 mg produced statistically significant deterioration.