Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder

To evaluate the efficacy, tolerability and safety of darifenacin, a once-daily M3) selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB). This multicentre, double-blind, placebo-controlled, parallel-group study enrolled 561 patients (19-88 years; 85% female) with OAB symptoms for >6 months, and included some patients with prior exposure to antimuscarinic agents. After washout and a 2-week placebo run-in, patients were randomised (1:4:2:3) to once-daily oral darifenacin controlled-release tablets (3.75 mg [n=53], 7.5 mg [229] or 15 mg [n=115]) or matching placebo (n=164) for 12 weeks. Patients recorded daily incontinence episodes, micturition frequency, bladder capacity (mean volume voided), frequency of urgency, severity of urgency, incontinence episodes resulting in change of clothing or pads and nocturnal awakenings due to OAB using an electronic diary during weeks 2, 6 and 12 (directly preceding clinic visits). Tolerability data were evaluated from adverse event reports. Darifenacin 7.5 mg and 15 mg had a rapid onset of effect, with significant improvement compared with placebo being seen for most parameters at the first clinic visit (week 2). This effect was sustained through week 12. At this time the number of incontinence episodes per week was reduced from baseline by 67.7% with darifenacin 7.5 mg and 72.8% with darifenacin 15 mg compared with 55.9% with placebo (p=0.010 and p=0.017, respectively, versus placebo). The 3.75 mg group (null dose arm) was included for proof of concept of dose flexibility, therefore formal sample sizing and statistical analysis were not performed for this group. Darifenacin 7.5 mg and 15 mg, respectively, were significantly superior to placebo for improvements in micturition frequency (p