Faculty Bibliography

OBJECTIVE: To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB). PATIENTS AND METHODS: In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for > or = 3 months and recorded > or = 8 voids and > or = 1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period. RESULTS: Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively. CONCLUSION: In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated

OBJECTIVE: Fesoterodine is an antimuscarinic agent indicated for the treatment of overactive bladder (OAB) symptoms. The objective of this study was to evaluate the efficacy of fesoterodine versus placebo over selected intervals during a 24-hour period in subjects with OAB. RESEARCH DESIGN AND METHODS: In a post hoc analysis, data were analyzed from two randomized, double-blind, placebo-controlled 12-week phase III trials in which subjects with a history of OAB symptoms for >or=6 months were treated with morning doses of fesoterodine 4 mg, fesoterodine 8 mg, or placebo. CLINICAL TRIAL REGISTRATION: These trials are registered at ClinicalTrials.gov (NCT00220363 and NCT00138723). MAIN OUTCOME MEASURES: Changes were evaluated in number of micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes, and mean voided volume (MVV) divided into three 8-hour intervals: 08:00-15:59 (daytime), 16:00-23:59 (evening), and 00:00-07:59 (nighttime). Comparisons with placebo were made using analysis of covariance (for least squares mean changes) and Wilcoxon rank sum test (for median percent changes); differences were considered significant at p < 0.05. RESULTS: Data from 1674 subjects, 80% of whom were women, were included in the analysis. At the end of treatment, the least squares mean change from baseline for all efficacy endpoints was significantly greater with fesoterodine 4 mg and fesoterodine 8 mg compared with placebo during each 8-hour time interval (all p < 0.05). Median percent change in number of micturitions, urgency episodes, and UUI episodes also was significantly greater with both fesoterodine doses compared with placebo during all time intervals (all p < 0.05). CONCLUSIONS: Fesoterodine 4 mg and 8 mg given once daily demonstrated efficacy over placebo for OAB symptoms during all three 8-hour intervals of a 24-hour period, thus providing clinical support for once-daily dosing. Limitations include that this was a post hoc analysis

Improvements in overactive bladder (OAB) symptoms and health-related quality of life (HRQL) were assessed during a 24-week study of tolterodine extended release (TOL ER) in sexually active women with OAB and urgency urinary incontinence (UUI). A 12-week, double-blind, randomized, placebo-controlled trial was followed by a 12-week open-label phase. Sexually active women reported symptoms for >/=3 months. Subjects completed bladder diaries and HRQL measures at baseline and weeks 12 and 24. One hundred sixty-one women received TOL ER for 24 weeks. Women reported significant improvements in all end points at week 12 that were maintained or improved at 24 weeks. At week 24, 70% of subjects reported no UUI episodes. TOL ER resulted in improvements in OAB symptoms and HRQL that were maintained or greater with 6 months of use. Long-term compliance with OAB pharmacotherapy may be important for optimal treatment outcomes

OBJECTIVE: To assess the effects of tolterodine extended release (ER) on patient-reported outcomes (PROs) in sexually active women with overactive bladder (OAB) and urgency urinary incontinence (UUI). RESEARCH DESIGN AND METHODS: This multicenter, double-blind, placebo controlled trial included 411 women aged > or =18 years reporting OAB symptoms for > or =3 months; > or =8 micturitions per 24 hours (including > or =0.6 UUI episodes and > or =3 OAB micturitions) in 5-day bladder diaries at baseline, and being in a sexually active relationship for > or =6 months. Subjects randomized to placebo or tolterodine ER completed validated OAB- or incontinence-specific questionnaires, including the Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), Urgency Perception Scale (UPS), and the Incontinence Impact Questionnaire (IIQ) at baseline and week 12, as well as the Perception of Treatment Benefit and Treatment Satisfaction questions at week 12. This study is registered with ClinicalTrials.Gov (identifier: NCT00143481). RESULTS: The mean age of enrolled women was approximately 48 years. Compared with placebo, the tolterodine ER group reported significant baseline to week 12 improvements in PPBC responses (p = 0.0048); OAB-q Symptom Bother, total Health-Related Quality of Life (HRQL), and HRQL domain scores (all p < 0.05); IIQ Emotional Health domain scores (p < 0.05); proportions of subjects reporting treatment benefit (79 vs. 54%; p < 0.0001) and satisfaction (78 vs. 59%; p < 0.0001). Improvements on the UPS were not significantly different. CONCLUSIONS: Tolterodine ER treatment was associated with improvements in multiple OAB- and incontinence-specific PROs in a sexually active, relatively young, and racially diverse population of women. The findings provide clinicians with new insights into the impact of OAB and its treatment on HRQL in this population, which has been underrepresented in previous OAB studies. Study limitations include a potential underestimation of the impact of OAB symptoms resulting from the exclusion of women who may not be sexually active because of their urinary symptoms

INTRODUCTION AND HYPOTHESIS: We assessed fesoterodine efficacy and tolerability in women with overactive bladder (OAB). METHODS: This post hoc analysis of pooled data from two clinical trials included 1,548 women with OAB randomized to placebo, fesoterodine 4 or 8 mg, or tolterodine extended release (ER) 4 mg (in 1 trial) for 12 weeks. Subjects completed 3-day bladder diaries at baseline and weeks 2 and 12 and rated Treatment Response at weeks 2 and 12. RESULTS: By weeks 2 and 12, all active-treatment groups showed significant improvements in all five bladder diary variables assessed and greater Treatment Response rates vs placebo. Fesoterodine 8 mg was significantly more efficacious than fesoterodine 4 mg and tolterodine ER in improving urgency urinary incontinence episodes and continent days per week. The most common adverse events were dry mouth and constipation, which were predominately mild or moderate. CONCLUSIONS: Fesoterodine is efficacious and well tolerated in women with OAB

We evaluated overactive bladder (OAB) symptoms and sexual and emotional health in sexually active women with OAB/urgency urinary incontinence (UUI) treated with tolterodine extended release (ER). Sexually active women with OAB symptoms were randomized to placebo or tolterodine ER. Five-day bladder diaries, Sexual Quality of Life Questionnaire-Female (SQOL-F), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ), and Hospital Anxiety and Depression Scale (HAD) were completed at baseline and week 12. Tolterodine ER (n = 201; mean +/- SD age, 49 +/- 12 years) reduced UUI episodes (P = 0.0029), total (P = 0.0006) and OAB (P < 0.0001) micturitions, and pad use per 24 h (P = 0.0024), and was associated with improvements in SQOL-F (P = 0.004), PISQ total (P = 0.009), and HAD Anxiety (P = 0.03) scores versus placebo (n = 210; mean +/- SD age, 47 +/- 12 years). OAB symptoms improved with tolterodine ER as did the scores of sexual health and anxiety measures in sexually active women with OAB