Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head‐to‐head, placebo‐controlled trial

• Published in: BJU international Vol. 107; no. 9; pp. 1432 - 1440
• Main Authors: Kaplan, Steven A., Schneider, Tim, Foote, Jenelle E., Guan, Zhonghong, Carlsson, Martin, Gong, Jason
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011; Wiley-Blackwell
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; antimuscarinic; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - therapeutic use; Biological and medical sciences; Cresols - administration & dosage; Cresols - therapeutic use; Delayed-Action Preparations; efficacy; Epidemiologic Methods; Female; fesoterodine; head‐to‐head; Humans; Male; Medical sciences; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - therapeutic use; Nephrology. Urinary tract diseases; Phenylpropanolamine - administration & dosage; Phenylpropanolamine - therapeutic use; Quality of Life; tolterodine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive - complications; Urinary Bladder, Overactive - drug therapy; Urinary Incontinence, Urge - drug therapy; Urinary Incontinence, Urge - etiology; Young Adult; Nephrology; Head; Treatment efficiency; Slow release form; Tolterodine; Fesoterodine; Urology; efficacy; Quality of life; Prospective; Anticholinergic agent; Cholinergic receptor; Age of onset; head-to-head; Antimuscarinic agent; antimuscarinic; Placebo; Clinical trial; Muscarinic receptor; Antagonist
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/j.1464-410X.2010.09640.x

Study Type – Therapy (RCT) 
Level of Evidence 1b What’s known on the subject? and What does the study add? A previous trial found greater efficacy with the maximum available dose of fesoterodine 8 mg compared with the maximum available dose of tolterodine ER 4 mg and placebo for improving overactive bladder symptoms, and patient‐reported outcomes were demonstrated by a recent placebo‐controlled, head‐to‐head trial. The results of this trial, the largest to date to compare antimuscarinic efficacy, confirms the superior efficacy of fesoterodine 8 mg over tolterodine ER 4 mg for the treatment of OAB symptoms, and further emphasize the clinical advantage of the availability of an additional 8‐mg dose over single‐dose tolterodine ER 4 mg. OBJECTIVE • To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo‐controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient‐reported outcomes. MATERIALS AND METHODS • In this 12‐week, double‐blind, double‐dummy trial, subjects reporting >1 urgency urinary incontinence (UUI) episode and ≥8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. • Subjects completed 3‐day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12. RESULTS • A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P < 0.05). • Superiority of fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P < 0.05). Dry mouth and constipation rates were 28% and 4% with fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo. • Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively. CONCLUSIONS • In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self‐reported patient assessments of bladder‐related problems, urgency, symptom bother and health‐related quality of life. • The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important implications for the clinical management of OAB patients previously treated with tolterodine ER.