Jon D. Morrow

Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial.

Study Type – Therapy (RCT)
Level of Evidence 1b

Randomized, Double-blind, Placebo-controlled Trial of Flexible-dose Fesoterodine in Subjects With Overactive Bladder

OBJECTIVES To evaluate the efficacy and tolerability of flexible-dose fesoterodine vs placebo in subjects with overactive bladder (OAB). METHODS In a 12-week double-blind trial, subjects were randomized to fesoterodine 4 mg or placebo once daily, taken within 4 hours of bedtime. At week 2, subjects could increase the fesoterodine dose to 8 mg (sham escalation for placebo). Subjects completed 3-day bladder diaries, Patient Perception of Bladder Condition, and Urgency Perception Scale at baseline and weeks 2, 6, and 12 as well as OAB Questionnaire at baseline and week 12. RESULTS Of 883 subjects, 63% and 73% of the fesoterodine (n = 438) and placebo (n = 445) groups, respectively, opted for dose escalation. Week 12 improvements from baseline in total micturitions, urgency episodes, urgency urinary incontinence episodes, frequency-urgency sum, and all OAB Questionnaire scales and domains, but not nocturnal micturitions or nocturnal urgency episodes, were significantly greater with fesoterodine than placebo (all P <.05). Treatment differences in micturitions and frequency-urgency sum were significant by week 2 and in urgency urinary incontinence and urgency episodes by week 6. Significantly greater percentages of subjects taking fesoterodine had improved Patient Perception of Bladder Condition and Urgency Perception Scale scores at weeks 2, 6, and 12 (P <.05). Dry mouth (fesoterodine, 26%; placebo, 8%) and constipation (fesoterodine, 11%; placebo, 6%) were the most common adverse events. In both groups, 87% of the subjects completed the trial; 8% and 5% of the fesoterodine and placebo groups, respectively, discontinued because of an adverse event. CONCLUSIONS Flexible-dose fesoterodine was efficacious and generally well tolerated for treatment of OAB symptoms.

Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.

Aims:  To evaluate the efficacy and tolerability of flexible‐dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.

Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.

To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible‐dose study.

Efficacy and tolerability of fesoterodine versus tolterodine in older and younger subjects with overactive bladder: A post hoc, pooled analysis from two placebo-controlled trials†‡

To assess the efficacy and tolerability of fesoterodine 8 mg versus tolterodine extended release (ER) 4 mg in subjects with overactive bladder (OAB) stratified by age (<65, 65–74, and ≥75 years).

Patient‐optimized doses of fesoterodine improve bladder symptoms in an open‐label, flexible‐dose study

Study Type – Therapy (cohort)

Early onset of fesoterodine efficacy in subjects with overactive bladder

Study Type – Therapy (cohort) Level of Evidence 2b

Effects of tolterodine ER on patient-reported outcomes in sexually active women with overactive bladder and urgency urinary incontinence

ABSTRACT 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 ≥18 years reporting OAB symptoms for ≥3 months; ≥8 micturitions per 24 hours (including ≥0.6 UUI episodes and ≥3 OAB micturitions) in 5-day bladder diaries at baseline, and being in a sexually active relationship for ≥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. Trial registration: ClinicalTrials.gov identifier: NCT00143481.

Efficacy of fesoterodine over 24 hours in subjects with overactive bladder

Abstract 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 ≥6 months were treated with morning doses of fesoterodine 4 mg, fesoterodine 8 mg, or placebo. Clinical trial registration: Trial registration: ClinicalTrials.gov identifier: NCT00220363. Trial registration: ClinicalTrials.gov identifier: 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.

The effect of elective sham dose escalation on the placebo response during an antimuscarinic trial for overactive bladder symptoms.

PURPOSE We analyzed the effects of baseline symptom severity and placebo response magnitude on the decision to dose escalate in a 12-week, randomized, double-blind, flexible dose antimuscarinic trial of subjects with overactive bladder symptoms. MATERIALS AND METHODS Data from the placebo arm of the trial were used for this post hoc analysis. Subjects could elect dose escalation at week 2. Those in the placebo arm received sham escalation. RESULTS Most placebo treated subjects who continued to week 2 elected dose escalation (75% or 325 of 435). Overactive bladder symptoms at baseline were similar between placebo escalators and nonescalators. Nonescalators showed a significantly larger placebo response than escalators, as measured by improvements in bladder diary end points and patient reported outcomes, and by the incidence rate of adverse events before and after sham escalation. CONCLUSIONS These findings suggest that the decision to dose escalate among placebo treated subjects is independent of baseline symptom severity but may be influenced by the placebo response magnitude for efficacy assessment and adverse events. Placebo nonescalators showed a rapid, large placebo response while placebo escalators showed a smaller placebo response even after sham escalation. These observations may have important implications for the design and interpretation of flexible dose trials using a placebo control.