Investigational OAB agent found safe, effective in phase II study

September 1, 2005

Results of a U.S. phase II trial investigating the safety, tolerability, and efficacy of the nonselective muscarinic antagonist fesoterodine fumarate in patients with detrusor overactivity offer hope for the 10% of men and women over age 40 years who have the syndrome, researchers say.

Results of a U.S. phase II trial investigating the safety, tolerability, and efficacy of the nonselective muscarinic antagonist fesoterodine fumarate in patients with detrusor overactivity offer hope for the 10% of men and women over age 40 years who have the syndrome, researchers say.

The randomized, double-blind, placebo-controlled trial conducted in 173 patients was conducted over an 8-week period by research teams at multiple institutions. After 1 week of placebo run-in, patients were randomized to placebo or to one of three once-daily doses of fesoterodine: 4 mg, 8 mg, or 12 mg. Primary endpoints were safety, efficacy, and tolerability of the agent.

Multiple regression analysis showed statistically significant linear dose-response improvement in the primary efficacy variable (number of micturitions in 24 hours) from baseline for the treatment groups versus placebo (p=.0449). Similar improvement was seen in the mean number of urge incontinence episodes per week, where a dose-response relationship was evident in the treatment groups compared with placebo: -5.9 episodes per week for the 4-mg dose group; -9.4 for the 8-mg group; and -8.1 for the 12-mg group.

"All three doses of fesoterodine led to significant and clinically relevant improvements from baseline in several parameters," said the authors, led by Victor Nitti, MD, associate professor of urology at New York University Medical Center. "Improvements were seen as early as 2 weeks after randomization."

Fesoterodine was generally well tolerated. Adverse events in the treatment groups were comparable with those for the placebo group. The most common adverse event was dry mouth. Overall, the percentage of patients who rated their tolerance as good or excellent were 86%, 87%, and 66% in the festoerodine 4 mg, 8 mg, and 12 mg groups, respectively.

Separately, the study's authors found that treatment response to fesoterodine in patients with overactive bladder was not influenced by urodynamic characterization.