Efficacy and safety of fesoterodine 8 mg in subjects with overactive bladder after a suboptimal response to tolterodine ER

Abstract

Aims: To assess fesoterodine 8 mg efficacy over time and vs. placebo in subjects with overactive bladder (OAB) who responded suboptimally to tolterodine extended release (ER) 4 mg.

Methods: In a 12-week, double-blind trial, subjects with self-reported OAB symptoms for ≥ 6 months, mean of ≥ 8 micturitions and ≥ 2 to < 15 urgency urinary incontinence (UUI) episodes/24 h, and suboptimal response to tolterodine ER 4 mg (defined as ≤ 50% reduction in UUI episodes during 2-week run-in) were randomised to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks) or placebo once daily. Change from baseline to week 12 in UUI episodes (primary end-point) was analysed in step-wise fashion: first, baseline vs. week 12 for fesoterodine; if significant, then change from baseline to week 12 for fesoterodine vs. placebo.

Results: By week 12, subjects receiving fesoterodine 8 mg had significantly greater improvement from baseline vs. placebo in UUI episodes, urgency episodes and scores on the Patient Perception of Bladder Control, Urgency Perception Scale and OAB Questionnaire Symptom Bother and Health-Related Quality of Life scales and domains (all p < 0.05). 50% and 70% UUI responder rates were also significantly higher with fesoterodine 8 mg vs. placebo at week 12 (p < 0.05). Dry mouth (placebo, 4%, 12/301; fesoterodine, 16.6%, 51/308) and constipation (placebo, 1.3%, 4/301; fesoterodine, 3.9%, 12/308) were the most frequent adverse events.

Conclusions: Subjects who responded suboptimally to tolterodine ER 4 mg showed significant improvements in UUI and other OAB symptoms and patient-reported outcomes, with good tolerability, during treatment with fesoterodine 8 mg vs. placebo.

Trial registration: ClinicalTrials.gov NCT01302054.

© 2014 The Authors International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Figures

Figure 1

Subject disposition. Full analysis set (FAS) = all randomised subjects who received ≥ 1 dose of study drug and had ≥ 1 efficacy assessment. Safety population = all randomised subjects who received ≥ 1 dose of double-blind study medication and/or took tolterodine ER in the run-in period. Sample size was determined from a subset of data from two of the fesoterodine Phase 3 studies that included subjects previously on tolterodine ER 4 mg with a change in UUI from baseline week 0 to week 2 ≤ 50% (non-responders) and a week 0 UUI value ≥ 2. Sample size was calculated using a two-sample t test to compare fesoterodine 8 mg and placebo (0.05 2-sided significance level). A sample size of 226 in each arm would have > 90% power to detect a difference in mean change from baseline in UUI episodes of −0.98 if the common standard deviation was 3.0, as observed previously. The within-group mean change from baseline to week 12 for fesoterodine 8 mg arm was expected to be no less than that of 8 mg vs. placebo, and thus this sample size had ≥ 90% power to detect a difference in frequency of UUI episodes.

Figure 2

Changes from baseline to weeks 4 and 12 in diary variables. (A) UUI episodes/24 h; (B) diary-dry rate; (C) micturitions/24 h; (D) urgency episodes/24 h; (E) 50% responder rates; (F) 70% responder rates. *p < 0.05; †p < 0.01.

Figure 3

Patient-reported outcomes at week 12. (A) PPBC; (B) UPS; (C) OAB-q. *p < 0.05; †p < 0.01; ‡p < 0.001.