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

Pooled Analysis of Two Open-Label Extension Studies

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Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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 8mg 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 un-expected 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.

Conclusions: Long-term fesoterodine (administered primarily as 8 mg) was well tolerated and associated with sustained improvements in OAB symptoms, irrespective of age.

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Acknowledgements

Funding for both extension studies was provided by Schwarz BioSciences GmbH and Pfizer Inc. Schwarz BioSciences GmbH participated in the design and conduct of the studies; Pfizer Inc. was involved in data analysis and manuscript preparation. Editorial assistance was provided by Nancy Sheridan and Colin Mitchell, PhD, from Complete Healthcare Communications, Inc., and was funded by Pfizer Inc.

Author’s Contributions: All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors participated in study concept and design, interpretation of data, drafting, and revising the article, and all have given final approval for the manuscript to be published. Other author contributions were as follows: acquisition of data: P.K.S., S.R.K. and J.H.; statistical analysis: M.C.

Conflicts of Interest: P.K.S. has been an advisor and speaker for Allergan, Astellas, GlaxoSmithKline, Ortho, Pfizer, Teva and Watson, and has received research grants from Allergan, Antares, Contura, Bioform, Boston Scientific, Ortho, Pfizer and Watson. J.H. has been an advisor and speaker for Allergan, Astellas, Pfizer and Uroplasty, and has received grants from Astellas, Medtronic, Pfizer and Pohl Boskamp. S.R.K. has been a consultant and lecturer for Pfizer and Laborie and has received research grants from Pfizer and the National Institute of Diabetes and Digestive and Kidney Diseases. M.C. and Z.G. are employees of Pfizer. S.B. was an employee of Pfizer at the time this study was conducted.

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Authors and Affiliations

  1. NorthShore University HealthSystem, Evanston Continence Center, University of Chicago, Pritzker School of Medicine, 1000 Central Street, Suite 730, Evanston, IL, 60201, USA

    Peter K. Sand

  2. Nijmegen Medical Centre, Radboud University, Nijmegen, the Netherlands

    John Heesakkers

  3. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Stephen R. Kraus

  4. Pfizer Inc., New York, NY, USA

    Martin Carlsson, Zhonghong Guan & Sandra Berriman

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  1. Peter K. Sand
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Correspondence to Peter K. Sand.

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Sand, P.K., Heesakkers, J., Kraus, S.R. et al. Long-Term Safety, Tolerability and Efficacy of Fesoterodine in Subjects with Overactive Bladder Symptoms Stratified by Age. Drugs Aging 29, 119–131 (2012). https://doi.org/10.2165/11597970-000000000-00000

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