A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M selective receptor antagonist, in the treatment of overactive bladder.

摘要

An international group of authors present a pooled analysis of data from their phase III multicentre double-blind clinical trials in patients with overactive bladder, which evaluated the efficacy, tolerability and safety of darifenacin. They found the drug, a muscarinic M(3) selective receptor antagonist, to be effective in the treatment of this condition, with excellent tolerability and safety. A paper from Denmark compares the efficacy and safety of alfuzosin and tamsulosin in a large randomized, double-blind, placebo-controlled, multicentre study. There were similar improvements in urinary symptoms and maximum urinary flow with the two drugs compared to placebo, but the incidence of sexual function adverse events was higher with tamsulosin than placebo. OBJECTIVE To evaluate the efficacy, tolerability and safety of darifenacin, a muscarinic M(3) selective receptor antagonist (M(3) SRA), from an analysis of pooled data from three phase III, multicentre, double-blind clinical trials in patients with overactive bladder (OAB). PATIENTS AND METHODS After a 4-week washout/run-in period, 1059 adults (85% women) with symptoms of OAB (frequency and urgency with urge incontinence) for >/= 6 months were randomized to once-daily oral treatment with darifenacin (7.5 mg, 337; or 15 mg, 334) or matching placebo (388) for 12 weeks. Efficacy was evaluated using electronic patient diaries that recorded incontinence episodes (including those resulting in a change of clothing or pads), frequency and severity of urgency, voiding frequency, and bladder capacity (volume voided). Safety was evaluated by analysis of adverse events (AEs), withdrawal rates and laboratory tests. RESULTS Relative to baseline, 12 weeks of treatment with darifenacin resulted in a significant reduction in the median (% change, interquartile range) number of incontinence episodes per week; 7.5 mg (-8.8, -68.4%, -15.1 to -4.4); 15 mg; (-10.6, -76.8%, -17.3 to -5.8: both P < 0.01 vs placebo). There was a significant dose-response trend in each study forwhich darifenacin 7.5 and 15 mg were evaluated (P < 0.01). There were also significant decreases in the frequency and severity of urgency, voiding frequency, and number of significant leaks (incontinence episodes resulting in a change of clothing or pads; both P