In treating nocturia related to urgency, flexible-dose fesoterodine (Toviaz) demonstrates statistical superiority to placebo in several areas, according to a study presented at the AUA annual meeting here.
Atlanta-In treating nocturia related to urgency, flexible-dose fesoterodine (Toviaz) demonstrates statistical superiority to placebo in several areas, according to a study presented at the AUA annual meeting here.
The large, double-blind, placebo-controlled study randomized 937 patients to once-daily placebo or flexible-dose fesoterodine for 12 weeks. Fesoterodine treatment was initiated at 4 mg, once daily and could be increased to 8 mg at the 4-week visit if needed.
The fesoterodine and control groups were similar in their baseline demographics and OAB symptoms. Nearly all nocturic micturitions were associated with urgency, and mean nocturnal urgency episodes/24 hours was close to three in both study groups.
Adverse event profile similar to placebo
Safety data showed the antimuscarinic drug was well tolerated and had a treatment-emergent adverse event profile similar to placebo, including for urinary retention, which occurred at a very low rate in the fesoteridine group (0.6%), reported first author Jeffrey P. Weiss, MD, professor and chair of urology at State University of New York Downstate Medical School, Brooklyn.
"Nocturnal urgency is a common problem. Until now, however, only post hoc analyses of OAB study data have been done to check for a possible effect of antimuscarinic drugs in treating nocturia, and generally, the results show no to minimal clinical benefit," Dr. Weiss said. "However, a signal for efficacy in a study of extended-release tolterodine (Detrol LA) provided the impetus for conducting a prospective, rigorously designed, adequately powered study investigating fesoterodine, which, like tolterodine, is a prodrug for the active metabolite, 5-hydroxymethyl tolterodine, but with an advantage of flexible dosing.
"Balancing the consistency of all of the efficacy outcomes in this large, randomized, placebo-controlled study with the safety data supports the conclusion that fesoteridine is a reasonable treatment choice for OAB patients with nocturnal urgency."
Prior to randomization, patients underwent a 2-week screening period and a 2-week, single-blind placebo run-in during which they kept 3-day micturition diaries. Eligible patients for randomization were adults self-reporting symptoms of OAB, including nocturnal urgency, of at least 3-months duration, who had a mean of ≥8 micturitions/24 hours, ≥3 urgency episodes/24 hours, and 2 to 8 nocturnal urgency episodes/24 hours (micturitions rated ≥3 on the Urinary Sensation Scale) during screening, and who during the run-in phase still had 2 to 8 micturition-related nocturnal urgency episodes/24 hours and a <35% decrease from screening in number of nocturnal urgency episodes/24 hours.
Dr. Weiss acknowledged that some urologists may question the clinical relevance of the modest absolute difference between the effects of fesoterodine and placebo in the various efficacy endpoints.
"Minimally important differences for treating nocturia have not been defined. However, it is generally felt that an improvement by at least one episode per night is something that patients can appreciate, and the effect of fesoterodine for improving nocturnal urgency episodes and nocturnal micturitions exceeded that threshold. Furthermore, fesoterodine demonstrated statistically significant superiority to placebo for improving symptom bother as well as in the individual health-related quality of life domains of the OAB-q, including sleep, and that consistency adds robustness to the data," he said.
"Certainly, there is a placebo effect in giving the antimuscarinic drug, but when treatment is needed for any condition, we give medications, not placebo. If clinicians want to prescribe a drug to treat OAB patients with complaints of nocturnal urgency, based on the study data, it appears rational to use fesoterodine."
Dr. Weiss is a consultant for Pfizer, Inc., Ferring Pharmaceuticals, Astellas Pharma, and Eli Lilly and Co.