Fesoterodine Treatment Research Articles

Long-Term Safety, Tolerability and Efficacy of Fesoterodine in Subjects with Overactive Bladder Symptoms Stratified by Age

Previous work has demonstrated the efficacy and safety of fesoterodine in older and younger subjects with overactive bladder (OAB) symptoms. The effect of long-term fesoterodine treatment in different age groups has not been assessed. The aim was to determine the impact of age on the safety, tolerability and efficacy of long-term treatment with fesoterodine 8 mg in subjects with OAB syndrome. This was a pooled analysis of two identically designed open-label extensions of 12-week, randomized, double-blind, placebo-controlled studies. The setting was urology and general practice offices. Subjects who participated in the 12-week, double-blind studies and opted to continue long-term, open-label treatment with fesoterodine were included. Subjects were initiated on fesoterodine 8 mg/day at open-label baseline. After 1 month, subjects could elect dose reduction to 4 mg/day and subsequent re-escalation to 8 mg; each was permitted once annually. Maximal duration of open-label treatment ranged from 24 to 36 months. Discontinuations, subject-reported treatment tolerance, and efficacy (3-day diaries) were assessed at open-label baseline and months 1, 4, 8, 12 and 24. A total of 890 subjects were treated (age <45 years, n = 140; 45-64 years, n = 444; 65-74 years, n = 208; ≥75 years, n = 98); 49% continued treatment for ≥ 24 months (age <45 years, 43%; 45-64 years, 54%; 65-74 years, 50%; ≥75 years, 37%). Seventy-seven percent of subjects remained on fesoterodine 8 mg throughout treatment; this rate was highest among subjects aged ≥75 years (age <45 years, 72%; 45-64 years, 77%; 65-74 years, 73%; ≥75 years, 87%). Approximately 80% of continuing subjects were receiving fesoterodine 8 mg at each visit after open-label baseline up to 36 months. No new or unexpected safety signals were observed in any age group. Most subjects reported 'good' or 'excellent' treatment tolerance throughout the study (age <45 years, ≥90%; 45-64 years, ≥93%; 65-74 years, ≥85%; ≥75 years, ≥86%). Dry mouth, the most commonly reported treatment-emergent adverse event, was lowest among subjects aged ≥75 years (age <45 years, 31%; 45-64 years, 30%; 65-74 years, 32%; ≥75 years, 26%). Rates of discontinuation due to dry mouth were low in all age groups. Significant improvements in all diary variables, including urgency urinary incontinence episodes per 24 hours, micturitions per 24 hours, urgency episodes per 24 hours, and mean voided volume per micturition, observed between double-blind baseline and open-label baseline were sustained or increased during open-label treatment in the overall population and all age groups. Long-term fesoterodine (administered primarily as 8 mg) was well tolerated and associated with sustained improvements in OAB symptoms, irrespective of age.

Sustained improvement in patient‐reported outcomes during long‐term fesoterodine treatment for overactive bladder symptoms: pooled analysis of two open‐label extension studies

• To evaluate the effects of long-term fesoterodine treatment on health-related quality of life (HRQL) and treatment satisfaction in subjects with overactive bladder (OAB) symptoms. • To determine the impact of gender and age on these effects. • This is a post hoc analysis of data pooled from identically designed open-label extensions of two randomized, double-blind, 12-week fesoterodine studies. • Initial treatment was once-daily fesoterodine 8 mg; subjects had the opportunity to receive open-label fesoterodine for ≥24 months. • After 1 month, subjects could elect dose reduction to 4 mg and subsequent re-escalation to 8 mg; dose reduction and re-escalation were each allowed once annually. • Changes in scores on the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and a Likert scale evaluating severity of bladder-related problems were assessed at open-label baseline and months 12 and 24; treatment satisfaction was assessed at open-label baseline and at months 4, 12 and 24. • A total of 864 enrolled subjects were included (men, n= 182; women, n= 682; aged <45 years, n= 134; 45-64 years, n= 432; 65-74 years, n= 204; ≥75 years, n= 94); most subjects (77%) who continued treatment maintained the 8-mg dose. • Among subjects in the overall population, there were significant improvements in all KHQ domains, ICIQ-SF scores, and bladder-related problems at open-label baseline vs double-blind baseline (P < 0.05); additional significant improvements were observed at months 12 and 24 vs open-label baseline in all outcomes (P < 0.05) except for the KHQ General Health Perception domain. • When data were stratified by gender or age, significant improvements at open-label baseline vs double-blind baseline were further significantly enhanced or sustained at months 12 and 24 for most KHQ domains, and for ICIQ-SF scores and bladder-related problems for all groups. Women had significantly greater improvements than men in the KHQ Emotion (P= 0.0173) and Severity/Coping (P= 0.0112) domains and ICIQ-SF scores (P= 0.0276) during open-label treatment. Subjects aged <45 years had significantly greater improvement in the Personal Relationships domain compared with those aged 45-64 years (P= 0.0357) and in the Sleep/Energy domain compared with all other groups (all P < 0.02). • Treatment satisfaction was high (≥92%) throughout open-label treatment regardless of gender or age. • Long-term fesoterodine treatment was associated with sustained improvement in measures of health-related quality of life and bladder-related problems and with high treatment satisfaction in subjects with overactive bladder symptoms. • Effects of gender and age were minimal.

Predictors of response to fesoterodine in patients with an overactive bladder

An analysis has been conducted of the predictors of the fesoterodine treatment response for female patients with overactive bladder (OAB) syndrome. Eighty-seven women diagnosed with OAB and who had undergone 12 weeks of treatment with fesoterodine (4 mg/day) were involved. Prior to treatment, the patients were evaluated through their medical history, physical examinations, urine analysis, urine cultures, voiding diaries and urodynamic studies. The voiding diaries and personal interviews concerning urinary symptoms were analyzed 12 weeks after treatment. Seventy-nine (82.3%) women experienced improvement of OAB symptoms (Improvement group), and for seventeen (17.7%) women the symptoms remained unchanged or worsened (Persistence group) after treatment. In the urodynamic studies, detrusor overactivity was noted in 37 (46.8%) patients of the improvement group and 3 (17.6%) of the persistence group. The number of patients who showed detrusor overactivity in urodynamic studies before the treatment was significantly larger in the improvement group. Maximum detrusor pressure and detrusor pressure at maximum flow were higher in the persistence group but not to statistically significant levels. In pre-treatment voiding diaries, the number of urgencies per day was significantly larger in the improvement group. The efficacy of fesoterodine treatment for female OAB problems was found to be be associated with the frequency of urgency and detrusor overactivity. Thus, both voiding diaries and urgency/detrusor symptom records may aid in predicting the efficacy of fesoterodine 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. Subjects were randomized to fesoterodine 4 mg or placebo. At week 2, subjects could remain on 4 mg (non-escalators) or choose to increase to 8 mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes. Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P < 0.001); at week 2, before dose escalation, diary-dry rate and improvement in micturitions and urgency episodes were significantly greater among fesoterodine non-escalators versus escalators (P < 0.001); and by week 12, after dose escalation, diary-dry rate and improvements in micturitions and UUI episodes were similar between fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point. A rapid and robust response to fesoterodine 4 mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8 mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8 mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose.

Long-term safety, tolerability, and efficacy of fesoterodine treatment in men and women with overactive bladder symptoms

Objective:To evaluate long-term safety, tolerability, and efficacy of fesoterodine for men and women with overactive bladder (OAB) symptoms.Research design and methods:This was a post hoc analysis of data pooled from two open-label extensions (NCT00220402, NCT00220376) of double-blind studies. All subjects began open-label treatment with fesoterodine 8 mg once daily, with voluntary dose reduction to 4 mg and re-escalation to 8 mg each permitted once annually. Maximum allowable duration of open-label treatment ranged from 24 to 36 months.Main outcome measures:Safety and discontinuations were assessed throughout treatment; subject-reported treatment tolerability and 3-day bladder diaries were evaluated at open-label baseline and months 1, 4, 8, 12, and 24.Results:A total of 185 men and 705 women enrolled; 83 men (45%) and 356 women (50%) continued open-label treatment for ≥24 months. Most men (84%) and women (75%) remained on fesoterodine 8 mg throughout open-label treatment. No new or unexpected safety signals were observed. Dry mouth was the most common treatment-emergent adverse event (men, 24%; women, 32%), rates of discontinuation due to dry mouth were low (men, 1%; women, 2%). Most men and women (≥91%) reported at least ‘good’ tolerance. For men and women, statistically significant improvements in urgency urinary incontinence episodes, micturitions, urgency episodes, and mean voided volume per micturition achieved between double-blind baseline and open-label baseline were sustained or further improved through month 24; significant improvements in most OAB symptoms were observed between double-blind baseline and month 24 when subjects were stratified by double-blind treatment (placebo, tolterodine extended release 4 mg, fesoterodine 4 mg, fesoterodine 8 mg). Limitations include the lack of a placebo control and that subjects completing double-blind treatment may have been more likely to tolerate or respond to long-term fesoterodine treatment.Conclusions:Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms in men and women.Trial registration: ClinicalTrials.gov identifier: NCT00220402.Trial registration: ClinicalTrials.gov identifier: NCT00220376.

Response to fesoterodine in patients with an overactive bladder and urgency urinary incontinence is independent of the urodynamic finding of detrusor overactivity

To determine whether the presence of detrusor overactivity (DO) in patients with overactive bladder (OAB) and urgency urinary incontinence (UUI) is a predictor of the response to treatment with fesoterodine. This phase 2 randomized, multicentre, placebo-controlled trial consisted of a 1-week placebo run-in phase followed by an 8-week double-blind period. Eligible for the study were men and women aged 18-78 years with symptoms or signs of OAB with UUI; they were stratified into two balanced strata depending on the outcome of a baseline urodynamic assessment. By using this particular study design it was possible to investigate whether there were differences between the strata. The primary endpoint was the change from baseline to week 8 in mean voids/24 h. Secondary endpoints were the changes in UUI episodes/week, and for those patients with DO at baseline, the mean changes in volume at first involuntary contraction associated with a feeling of urgency, first desire to void, and strong desire to void, and change in maximum cystometric capacity. Because there were few patients the secondary analyses were considered exploratory. Overall, there were linear dose-response relationships for placebo and the fesoterodine groups for the reduction in the number of voids/24 h and UUI episodes/week. Compared with the placebo group, the least squares mean changes from baseline to week 8 in both variables were significantly improved in patients receiving fesoterodine 4 mg (P = 0.045 and 0.040, respectively), 8 mg (P < 0.001 for both), and 12 mg (P < 0.001 for both). There were no significant differences in treatment responses, as measured by both variables between patients with and without DO. For patients with DO, the mean volume at the first desire to void improved in all fesoterodine treatment groups and worsened in the placebo group. Regardless of the presence of DO, the response to fesoterodine treatment was dose-proportional and associated with significant improvements in OAB symptoms, indicating that the response to OAB pharmacotherapy in patients with UUI was independent of the urodynamic diagnosis of DO.

Long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder symptoms

The aim of this study was to assess the long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder (OAB) symptoms. This was an open-label extension study of a 12-week, double-blind fesoterodine study. During open-label treatment, all subjects received fesoterodine 8 mg for an initial 4 weeks, after which subjects could elect dose reduction to 4 mg or subsequent reescalation to 8 mg during clinic visits (dose reduction and reescalation each permitted once annually). The maximum allowable duration of open-label fesoterodine treatment ranged from 24 to 32 months across study sites. Safety and tolerability were evaluated via discontinuations, fesoterodine exposure, treatment-emergent adverse events (TEAEs) and subject-reported treatment tolerance. Three-day bladder diaries and other patient-reported outcomes (PROs) were assessed during the first 24 months of open-label treatment. PROs included evaluations of health-related quality of life [HRQL; King's Health Questionnaire (KHQ), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)], severity of bladder-related problems and treatment satisfaction. Subjects completed 3-day diaries before open-label baseline and months 1, 4, 8, 12 and 24; the ICIQ-SF and measures of bladder-related problems and treatment satisfaction at open-label baseline and months 4, 12 and 24; and the KHQ at open-label baseline and months 12 and 24. Of the 417 eligible subjects who enrolled in the open-label extension, 61% continued fesoterodine treatment for > or = 24 months and 71% elected to maintain the fesoterodine 8-mg dose throughout treatment. No unexpected safety signals were observed. Most subjects rated treatment tolerance as at least 'good' throughout the study (> or = 88%). Dry mouth was the most commonly reported TEAE (34%) during open-label treatment, resulting in discontinuation in 2% of subjects (n = 8). Improvements from open-label baseline in OAB symptoms, HRQL and bladder-related problems were statistically significant at the earliest point measured and maintained through month 24. Treatment satisfaction rates were high throughout the study (> or = 84%). Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms and HRQL.