PMID- 15839920
OWN - NLM
STAT- MEDLINE
DCOM- 20050526
LR  - 20121115
IS  - 1464-4096 (Print)
IS  - 1464-4096 (Linking)
VI  - 95
IP  - 7
DP  - 2005 May
TI  - A pooled analysis of three phase III studies to investigate the efficacy, 
      tolerability and safety of darifenacin, a muscarinic M3 selective receptor 
      antagonist, in the treatment of overactive bladder.
PG  - 993-1001
AB  - OBJECTIVE: To evaluate the efficacy, tolerability and safety of darifenacin, a 
      muscarinic M3 selective receptor antagonist (M3 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 > or = 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 for which 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 < or = 0.001 vs 
      placebo), together with an increase in bladder capacity (both P < 0.01 vs 
      placebo). Darifenacin was well tolerated; the most common AEs were dry mouth and 
      constipation, although together these resulted in few discontinuations 
      (darifenacin 7.5 mg 0.6% of patients; 15 mg 2.1%; placebo 0.3%). The incidence of 
      peripheral/central nervous system and cardiovascular AEs were comparable with 
      those on placebo. CONCLUSIONS: Darifenacin (7.5 and 15 mg once daily) is 
      effective in the treatment of patients with OAB. As predicted by its M3 
      selectivity and associated M1/M2-sparing profile, darifenacin was well tolerated 
      with no central nervous system or cardiovascular safety concerns.
FAU - Chapple, Christopher
AU  - Chapple C
AD  - Urology Research, Royal Hallamshire Hospital, Sheffield, UK. 
      c.r.chapple@shef.ac.uk
FAU - Steers, William
AU  - Steers W
FAU - Norton, Peggy
AU  - Norton P
FAU - Millard, Richard
AU  - Millard R
FAU - Kralidis, Georg
AU  - Kralidis G
FAU - Glavind, Karin
AU  - Glavind K
FAU - Abrams, Paul
AU  - Abrams P
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Benzofurans)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptor, Muscarinic M3)
RN  - APG9819VLM (darifenacin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Benzofurans/*administration & dosage/adverse effects
MH  - Clinical Trials, Phase III as Topic
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multicenter Studies as Topic
MH  - Pyrrolidines/*administration & dosage/adverse effects
MH  - Randomized Controlled Trials as Topic
MH  - Receptor, Muscarinic M3/*antagonists & inhibitors
MH  - Treatment Outcome
MH  - Urinary Incontinence/*drug therapy
EDAT- 2005/04/21 09:00
MHDA- 2005/05/27 09:00
CRDT- 2005/04/21 09:00
PHST- 2005/04/21 09:00 [pubmed]
PHST- 2005/05/27 09:00 [medline]
PHST- 2005/04/21 09:00 [entrez]
AID - BJU5454 [pii]
AID - 10.1111/j.1464-410X.2005.05454.x [doi]
PST - ppublish
SO  - BJU Int. 2005 May;95(7):993-1001. doi: 10.1111/j.1464-410X.2005.05454.x.