Evaluation of cognitive function in healthy older subjects treated with fesoterodine

To evaluate the cognitive effects of fesoterodine 4 and 8 mg versus placebo in healthy older adults.

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.

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.

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.