Fesoterodine Dose Response in Subjects With Overactive Bladder Syndrome
Urology
vol. 71, 839 - 843, 2008
Abstract
Objectives:
To compare the efficacy of fesoterodine 4mg versus 8mg in treating subjects with overactive bladder (OAB) syndrome.
Methods:
This is a pooled analysis of data from 2 randomized placebo (PBO)-controlled phase III trials. Eligible subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to PBO or fesoterodine 4 or 8mg for 12 weeks. Subjects assessed efficacy using 3-day bladder diaries recording the time of each void, urgency, and incontinence episode. Endpoints included treatment response (based on a 4-point Treatment Benefit scale) and change from baseline in micturitions, UUI episodes, mean volume voided, urgency episodes, and continent days. We assessed tolerability and safety by evaluating adverse events, residual urine volume, laboratory parameters, and treatment withdrawals.
Results:
At the end of treatment, both doses of fesoterodine showed statistically significant improvements in all efficacy endpoints versus PBO (P<0.01). These effects were seen 2 weeks after initiation of treatment (the earliest evaluation point) and were sustained throughout the treatment period. Fesoterodine 8mg performed significantly better than fesoterodine 4mg in improving all diary variables (P<0.05) except micturition frequency, demonstrating a dose-response relationship. Adverse events reported more frequently with fesoterodine than with PBO included dry mouth, constipation, and urinary tract infection.
Conclusions:
Both fesoterodine 4 and 8mg are effective in improving OAB symptoms. The higher 8-mg dose provides additional benefit compared with the lower dose in improving most bladder diary variables, thus offering the possibility of dose flexibility and titration.
Commentary
= Suggested Reading
Articles that have been selected because they are important for safe, informed medical practice.
A: Evidence from an article that is shown in a human (double-blind, when appropriate), randomized trial, meta-analysis or both
Fesoterodine represents yet another antimuscarinic compound purported to treat overactive bladder. This compound may be considered a “prodrug” in that upon ingestion it is rapidly, completely, and irreversibly metabolized to the primary metabolite of tolterodine, currently the most widely prescribed overactive bladder agent in the United States. This may confer some favorable metabolic properties over the parent compound. This study suggests that there exists a true dose-response relationship between the 2 doses of this compound in most voiding diary parameters and other clinical outcome parameters. The clinical implication of this lies in the potential to improve efficacy with dose escalation in a meaningful fashion. Will this improve patient compliance in this therapeutic category, which is notoriously suboptimal? This will not be known for some time. Will this compound be superior to those already available for the overactive patient? Likewise, this will not be known until direct head to head studies are performed.
