title: Phase II study on the efficacy and safety of the EP1 receptor antagonist ONO-8539 for nonneurogenic overactive bladder syndrome.
abstract: OBJECTIVE
  We evaluated the efficacy, safety and tolerability of the EP1 receptor antagonist ONO-8539 in patients with overactive bladder syndrome.
  
  
  METHODS
  This was a 12-week, randomized, double-blind, placebo controlled, parallel group, multicenter study with a 2-week single blind placebo run-in phase. The 435 patients were randomized to receive twice daily ONO-8539 (30, 100 or 300 mg), placebo or once daily tolterodine (4 mg).
  
  
  RESULTS
  At the end of the 12-week treatment no statistically significant difference was found between ONO-8539 and placebo in the change from baseline in the number of micturitions per 24 hours. The primary end points for 30, 100 and 300 mg ONO-8539, and placebo were -1.02, -1.53, -1.31 and -1.40, respectively. There was no statistically significant difference between any ONO-8539 group and placebo in the change from baseline in the number of urgency or urinary urgency incontinence episodes per 24 hours, or the mean volume voided per micturition, which were secondary end points. Statistically significant differences for tolterodine vs placebo were observed in the change from baseline in the number of micturitions (p = 0.045), urgency episodes (p = 0.04) and mean volume voided per micturition (p <0.001). The incidence of adverse events was 54.1% in the placebo group, 43.0% to 54.0% in the ONO-8539 groups and 46.6% in the tolterodine group. The intensity of adverse events was similar among the treatment groups. Similar to other treatments, the most frequently reported adverse events after ONO-8539 were nasopharyngitis and diarrhea.
  
  
  CONCLUSIONS
  The results of this study, which to our knowledge represents the first evaluation of ONO-8539 in patients with overactive bladder, suggest a minimal role for EP1 receptor antagonism in the management of overactive bladder syndrome.
authors.affiliation: Royal Hallamshire Hospital, Sheffield, United Kingdom. Electronic address: c.r.chapple@sheffield.ac.uk.
authors.forename: C R
authors.initials: CR
authors.lastname: Chapple
authors.affiliation: Southmead Hospital, Bristol Urological Institute, Bristol, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Abrams
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: K-E
authors.initials: KE
authors.lastname: Andersson
authors.affiliation: Department of Urology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Radziszewski
authors.affiliation: ONO Pharma Ltd., London, United Kingdom.
authors.forename: T
authors.initials: T
authors.lastname: Masuda
authors.affiliation: ONO Pharma Ltd., London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Small
authors.affiliation: ONO Pharma Ltd., London, United Kingdom.
authors.forename: T
authors.initials: T
authors.lastname: Kuwayama
authors.affiliation: ONO Pharma Ltd., London, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Deacon
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003408:Cresols / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010665:Phenylpropanolamine / Q000627:therapeutic use*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors*; D000068737:Tolterodine Tartrate; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D064804:Urological Agents / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D058306:Receptors, Prostaglandin E, EP1 Subtype; D064804:Urological Agents; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate
keywords: ATP; EP1 subtype; LOCF; OAB; PG; UUI; adenosine triphosphate; last observation carried forward; overactive; overactive bladder; prostaglandin; prostaglandin E; receptors; treatment outcome; urge; urgency urinary incontinence; urinary bladder; urinary incontinence; urination