Dose response with darifenacin, a novel once-daily M3 selective receptor antagonist for the treatment of overactive bladder: results of a fixed dose study.
This study evaluated the efficacy, tolerability, and safety of darifenacin, an M3 selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB). In a multicenter, double-blind, placebo-controlled dose-ranging study, 439 adult OAB patients (85.4% female) were randomized to darifenacin controlled-release tablets 7.5 mg (n = 108), 15 mg (n = 107) or 30 mg (n = 115) qd, or placebo (n = 109) for 12 weeks. Darifenacin significantly reduced the median number of incontinence episodes/week (-68.7, -76.5, and -77.3% from baseline at 7.5, 15, and 30 mg, respectively, vs -46% with placebo, all p < 0.01) and dose relatedly improved micturition frequency, frequency and severity of urgency, nocturia, and bladder capacity. Darifenacin was well tolerated. Adverse events were commonly mild to moderate dry mouth and constipation. There were no safety concerns. Darifenacin is effective and well tolerated in the treatment of OAB, with 7.5 and 15 mg doses offering flexibility of dosing for optimal treatment outcome.
Department of Obstetrics and Gynaecology, Queen's Park Hospital, Haslingden Road, Blackburn, UK. simon.hill@mail.bhrv.nwest.nhs.uk
Simon
S
Hill
Vik
V
Khullar
Jean-Jacques
JJ
Wyndaele
Karine
K
Lheritier
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D012449:Safety; D013607:Tablets; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000517:prevention & control; D014554:Urination / Q000187:drug effects; D014555:Urination Disorders / Q000188:drug therapy / Q000517:prevention & control; D014987:Xerostomia / Q000139:chemically induced
D001572:Benzofurans; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D010919:Placebos; D011759:Pyrrolidines; D043587:Receptor, Muscarinic M3; D013607:Tablets; C101207:darifenacin