Efficacy and Safety of Flexible Dose Fesoterodine in Men and Women with Overactive Bladder Symptoms Including Nocturnal Urinary Urgency

Abstract

Purpose Awakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder. Materials and Methods Subjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided. The primary end point was change from baseline to week 12 in the mean number of micturition related nocturnal urgency episodes per 24 hours. Results Overall 963 subjects were randomized from 2,990 screened, and 82% of subjects treated with fesoterodine and 84% of those treated with placebo completed the study. Significant improvements in the primary end point (−1.28 vs −1.07), in nocturnal micturitions per 24 hours (−1.02 vs −0.85) and in nocturnal frequency urgency sum (−4.01 vs −3.42) were observed with fesoterodine vs placebo (all p ≤0.01). Health related quality of life measures (overactive bladder questionnaire Symptom Bother −20.1 vs −16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were improved with fesoterodine. Conclusions To our knowledge this is the first prospective study to assess antimuscarinic efficacy for reducing nocturnal urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency episodes vs placebo in subjects with overactive bladder.

Fesoterodine clinical efficacy and safety for the treatment of overactive bladder in relation to patient profiles: a systematic review

“…In a randomized, double-blind, placebo-controlled, flexible-dose, 12 week trial in 963 patients with OAB symptoms, including !3 urgency episodes/24 h and !2 and 8 nocturnal urgency episodes/24 h, a significantly greater decrease from baseline to week 12 in nocturnal urgency episodes/24 h (primary endpoint; fesoterodine, À1.3; placebo, À1.1; P ¼ 0.003) and nocturnal micturitions/24 h (P ¼ 0.011) was demonstrated with fesoterodine versus placebo 65 . This trial of fesoterodine was the first to prospectively evaluate the efficacy of an antimuscarinic for decreasing nocturnal urgency episodes.…”

“…In addition to the two open-label, flexible-dose, extension trials, a flexible-dosing design was used in three openlabel 50,67,77 and five double-blind 48,65,76,80,84 trials evaluating the efficacy and safety of fesoterodine.…”

Nocturia: an overview of evaluation and treatment

“…963 subjects with ≥ 2 nocturia episodes were randomized to receive either fesoterodine or placebo and followed for 12 weeks. Fesoterodine significantly reduced nocturnal urgency episodes over placebo (-1.28 vs -1.07, P = 0.003), as were nocturia episodes (-1.02 vs -0.85, P < 0.01) [28]. Further study of the newer antimuscarinics' efficacy in nocturia treatment is needed in order to demonstrate clinically significant efficacy.…”

Management of Nocturia in the Female

“…At the 2012 New England Research Institute (NERI) nocturia advisory conference, experts left open the possibility of using these medications to treat severe nocturnal OAB episodes [8••]. In a double-blind randomized controlled trial, the antimuscarinic agent fesoterodine was indeed found to have a statistically significant reduction in nocturnal urgency episodes compared to placebo, but the mean difference was only −0.21 [59]. There are several potential reasons for the lack of efficacy in treating nocturia-(1) decreased functional bladder capacity plays a minor role in the etiology of OAB-associated nocturia; (2) OAB is intrinsically too heterogeneous, thus, masking any clinically significant subset of responders; or (3) OAB medications do not sufficiently increase functional bladder capacity to result in clinical improvement.…”