Superiority of Fesoterodine 8 mg Versus Fesoterodine 4 mg in Reducing Urgency Urinary Incontinence Episodes in Subjects with Overactive Bladder: Results of the Randomized, Double-Blind, Placebo-Controlled EIGHT Trial
Chapple C1, Schneider T, Haab F, Sun F, Whelan L, Scholfield D, Dragon E, Mangan E. BJU Int. 2014 Feb 19. doi: 10.1111/bju.12678. [Epub ahead of print]

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1The Royal Hallamshire Hospital, Sheffield, United Kingdom.

Abstract

OBJECTIVE: To assess the superiority of fesoterodine 8 mg vs fesoterodine 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary-dry rate (proportion of subjects with >0 UUI episodes on baseline diary and 0 UUI episodes on postbaseline diary), and improvements in measures of symptom bother, health-related quality of life (HRQL), and other patient-reported outcomes.

SUBJECTS AND METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, multinational trial of men and women aged ≥18 years with OAB symptoms including UUI (ClinicalTrials.gov ID NCT01302067). Subjects were randomized (2:2:1) to receive fesoterodine 8 mg, fesoterodine 4 mg, or placebo once daily; subjects randomized to fesoterodine 8 mg started with 4 mg of fesoterodine once daily for 1 week then 8 mg once daily for the remaining 11 weeks. Subjects completed bladder diaries at baseline and weeks 4 and 12 and the Patient Perception of Bladder Condition (PPBC) , Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. The primary endpoint was change from baseline to week 12 in UUI episodes per 24 hours.

RESULTS: At week 12, subjects receiving fesoterodine 8 mg (n=779) had significantly greater reductions from baseline in UUI episodes, micturitions, and urgency episodes than subjects receiving fesoterodine 4 mg (n=790) or placebo (n=386) ; diary-rate was significantly higher in the fesoterodine 8-mg group vs the fesoterodine 4-mg and placebo groups (all P<0.05). At week 12, subjects receiving fesoterodine 8 mg also had significantly greater improvements in scores on the PPBC, UPS, and all OAB-q scales and domains than subjects receiving fesoterodine 4 mg or placebo (all P<0.01). Subjects receiving fesoterodine 4 mg had significantly greater improvements in UUI episodes, urgency episodes, and micturitions; significantly higher diary-dry rates; and significantly greater improvement in PPBC scores and OAB-q scores than subjects receiving placebo (all P<0.05). Dry mouth was the most commonly reported adverse event in the fesoterodine groups (placebo group, 3.4%; fesoterodine 4-mg group, 12.9%; fesoterodine 8-mg group, 26.1%); most cases were mild or moderate in all treatment groups. Rates of serious adverse events and discontinuations due to adverse events were low in all groups.

CONCLUSIONS: In a 12-week, prospectively-designed superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy versus fesoterodine 4 mg and placebo as measured by reductions in UUI episodes and other diary variables, diary-dry rate, and improvements in measures of symptom bother, HRQL, and other patient-reported outcomes; clear evidence of dose-dependent efficacy is unique to fesoterodine among antimuscarinics and other oral agents for the treatment of OAB . Fesoterodine 4 mg was significantly more effective than placebo on all outcomes except for improvements in UPS scores. These data support the benefit of having 2 doses of fesoterodine in clinical practice, with the recommended starting dose of 4 mg for all patients and the fesoterodine 8-mg dose available for patients who require a higher dose to achieve optimal symptom relief.