Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study.
OBJECTIVE
To examine, in a 2-year, non-comparative, open-label extension study, the safety, tolerability and efficacy of darifenacin controlled-release (CR) 7.5/15 mg once daily in patients with overactive bladder (OAB) who completed two 12-week randomized, double-blind, placebo-controlled 'feeder' studies.


METHODS
Patients entering the extension received darifenacin 7.5 mg once daily for 2 weeks, after which a voluntary increase in dose to 15 mg was permitted. Thereafter, patients could adjust the dose (either 7.5 or 15 mg). Safety and tolerability were assessed from adverse events (AEs) and discontinuations. Efficacy was determined using various endpoints.


RESULTS
In all, 716 patients entered the extension (mean age 57.3 years; 85.1% women) and 475 (66.3%) completed it (1089.9 patient-years of exposure). Darifenacin was well tolerated with no significant safety concerns. The most commonly reported AEs were dry mouth and constipation (all-causality rates 23.3% and 20.9%, respectively), leading to discontinuation in 1.3% and 2.4% of patients, respectively. Constipation infrequently required intervention, and analysis of bowel-habit questionnaires revealed that the reporting of constipation was related to minor changes in bowel habit rather than true constipation. The efficacy of darifenacin was maintained, including significant improvements in the number of incontinence episodes/week (median change -84.4% at 2 years, P < 0.001 vs feeder-study baseline). After 2 years, > 40% of patients achieved a > or = 90% reduction in incontinence episodes/week.


CONCLUSIONS
In the first published 2-year, open-label study of a CR antimuscarinic agent, darifenacin 7.5/15 mg once daily had a favourable safety, tolerability and efficacy profile during the long-term treatment of OAB. As such, darifenacin represents a valuable therapeutic option for OAB.
Haab
François
F
Départment d'Urologie, Hôpital Tenon, Paris, France. francois.haab@tnn.ap-hop-paris.fr
Corcos
Jacques
J
Siami
Paul
P
Glavind
Karin
K
Dwyer
Peter
P
Steel
Michael
M
Kawakami
Fernando
F
Lheritier
Karine
K
Steers
William D
WD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001572:Benzofurans / Q000008:administration & dosage* / Q000009:adverse effects; D003248:Constipation / Q000139:chemically induced; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014549:Urinary Incontinence / Q000188:drug therapy*; D014987:Xerostomia / Q000139:chemically induced
D001572:Benzofurans; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; C101207:darifenacin