title: Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity.
abstract: OBJECTIVE
  We assessed the efficacy, safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity.
  
  
  METHODS
  In this 52-week, international, multicenter, double-blind, randomized, placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence (14 or more episodes per week) resulting from multiple sclerosis (227) and spinal cord injury (189) were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo. The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6. Maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points. Adverse events were monitored.
  
  
  RESULTS
  OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week, respectively, vs 9 episodes per week in 149 on placebo (each dose p<0.001). Also, maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group (each dose p<0.001). Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo (256 and 254 days, respectively, vs 92). The most common adverse events were urinary tract infection and urinary retention. Of patients who did not catheterize at baseline 10% on placebo, 35% on 200 U and 42% on 300 U initiated catheterization due to urinary retention.
  
  
  CONCLUSIONS
  OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo. Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion. No clinically relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose.
authors.affiliation: Department of Urology, University of Southern California, Los Angeles, Norris Cancer Center, Los Angeles, CA 90033, USA. ginsberg@med.usc.edu
authors.forename: David
authors.initials: D
authors.lastname: Ginsberg
authors.forename: Angelo
authors.initials: A
authors.lastname: Gousse
authors.forename: Veronique
authors.initials: V
authors.lastname: Keppenne
authors.forename: Karl-Dietrich
authors.initials: KD
authors.lastname: Sievert
authors.forename: Catherine
authors.initials: C
authors.lastname: Thompson
authors.forename: Wayne
authors.initials: W
authors.lastname: Lam
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Brin
authors.forename: Brenda
authors.initials: B
authors.lastname: Jenkins
authors.forename: Cornelia
authors.initials: C
authors.lastname: Haag-Molkenteller
mesh_terms: D000328:Adult; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D009465:Neuromuscular Agents / Q000008:administration & dosage*; D011788:Quality of Life; D013119:Spinal Cord Injuries / Q000150:complications*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology*; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000209:etiology
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A