A randomized, double-blind, placebo-controlled phase II dose-finding study of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder.
OBJECTIVE
To evaluate the efficacy, safety/tolerability, and dose-response relationship of imidafenacin in Japanese patients with overactive bladder.


METHODS
Men and women who had overactive bladder symptoms were randomized equally to double-blind treatment with 0.05, 0.1, or 0.25 mg of imidafenacin twice daily or a placebo for 12 weeks, and assessed for efficacy and safety.


RESULTS
Overall, 401 patients were enrolled and randomized for treatment with 0.1 mg of imidafenacin/day (99 patients), 0.2 mg of imidafenacin/day (100), 0.5 mg of imidafenacin/day (101), or a placebo (101). After 12 weeks of treatment, the number of incontinence episodes was reduced in a dose-dependent manner, and a significant difference between the imidafenacin treatment and the placebo was observed (P < 0.0001). Compared with the placebo, imidafenacin caused significant reductions in urgency incontinence, voiding frequency, and urinary urgency, and a significant increase in the urine volume voided per micturition. Imidafenacin was also well tolerated. The incidence of dry mouth in the imidafenacin groups increased dose-dependently. Even though the percentage of patients receiving 0.5 mg/day who discontinued treatment due to dry mouth was high (8.9%), the percentages in the 0.1 mg/day and 0.2 mg/day groups (1.0% and 0.0%, respectively) were comparable with that in the placebo group (0.0%).


CONCLUSIONS
Considering the balance between efficacy and safety, 0.1 mg of imidafenacin twice daily appeared to be a clinically appropriate dose for treating overactive bladder. This dose was therefore selected for further evaluation in large-scale phase III studies.
Homma
Yukio
Y
Department of Urology, University of Tokyo, Tokyo, Japan.
Yamaguchi
Takuhiro
T
Yamaguchi
Osamu
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007564:Japan; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D055815:Young Adult
D007093:Imidazoles; D018727:Muscarinic Antagonists; C120953:imidafenacin