OBJECTIVE: To assess the superiority of fesoterodine 8 mg vs 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary-dry rate (proportion of patients with >0 UUI episodes on baseline diary and 0 UUI episodes on post-baseline diary), and improvements in measures of symptom bother, health-related quality of life (HRQL), and other patient-reported outcomes (PROs). PATIENTS AND METHODS: This was a 12-week, randomised, double-blind, placebo-controlled, multinational trial of men and women aged ≥18 years with overactive bladder (OAB) symptoms including UUI (ClinicalTrials.gov ID NCT01302067). Patients were randomised (2:2:1) to receive fesoterodine 8 mg, fesoterodine 4 mg, or placebo once daily; those randomised to fesoterodine 8 mg started with fesoterodine 4 mg once daily for 1 week, then 8 mg once daily for the remaining 11 weeks. Patients 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 h. RESULTS: At week 12, patients receiving fesoterodine 8 mg (779 patients) had significantly greater reductions from baseline in UUI episodes, micturitions, and urgency episodes than patients receiving fesoterodine 4 mg (790) or placebo (386); diary-dry 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, patients receiving fesoterodine 8 mg also had significantly greater improvements in scores on the PPBC, UPS, and all OAB-q scales and domains than patients receiving fesoterodine 4 mg or placebo (all P < 0.01). Patients 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 patients receiving placebo (all P < 0.05). Dry mouth was the most commonly reported adverse event (AE) 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 AEs and discontinuations due to AEs were low in all groups. CONCLUSIONS: In a 12-week, prospectively designed, superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy vs fesoterodine 4 mg and placebo, as measured by reductions in UUI episodes and other diary variables, diary-dry dry rate, and improvements in measures of symptom bother, HRQL, and other PROs; 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 two 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.
RCT Entities:
OBJECTIVE: To assess the superiority of fesoterodine 8 mg vs 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary-dry rate (proportion of patients with >0 UUI episodes on baseline diary and 0 UUI episodes on post-baseline diary), and improvements in measures of symptom bother, health-related quality of life (HRQL), and other patient-reported outcomes (PROs). PATIENTS AND METHODS: This was a 12-week, randomised, double-blind, placebo-controlled, multinational trial of men and women aged ≥18 years with overactive bladder (OAB) symptoms including UUI (ClinicalTrials.gov ID NCT01302067). Patients were randomised (2:2:1) to receive fesoterodine 8 mg, fesoterodine 4 mg, or placebo once daily; those randomised to fesoterodine 8 mg started with fesoterodine 4 mg once daily for 1 week, then 8 mg once daily for the remaining 11 weeks. Patients 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 h. RESULTS: At week 12, patients receiving fesoterodine 8 mg (779 patients) had significantly greater reductions from baseline in UUI episodes, micturitions, and urgency episodes than patients receiving fesoterodine 4 mg (790) or placebo (386); diary-dry 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, patients receiving fesoterodine 8 mg also had significantly greater improvements in scores on the PPBC, UPS, and all OAB-q scales and domains than patients receiving fesoterodine 4 mg or placebo (all P < 0.01). Patients 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 patients receiving placebo (all P < 0.05). Dry mouth was the most commonly reported adverse event (AE) 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 AEs and discontinuations due to AEs were low in all groups. CONCLUSIONS: In a 12-week, prospectively designed, superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy vs fesoterodine 4 mg and placebo, as measured by reductions in UUI episodes and other diary variables, diary-dry dry rate, and improvements in measures of symptom bother, HRQL, and other PROs; 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 two 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.