title: Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome.
abstract: BACKGROUND
  Neurokinin receptors may play an important role in the visceral hypersensitivity and exaggerated motor/secretory activity associated with diarrhoea-predominant irritable bowel syndrome (IBS-D).
  
  
  OBJECTIVE
  To evaluate the effects of DNK333, a novel neurokinin antagonist, in women with IBS-D.
  
  
  METHODS
  In two consecutive phase II studies, women with IBS-D were randomised to twice-daily (b.d.) DNK333 25 mg, DNK333 100 mg or placebo for 2 weeks (Trial 1), or DNK333 25 mg b.d. or placebo for 4 weeks (Trial 2). Primary efficacy variables studied were change from baseline of stool form at week 2, and satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Secondary efficacy variables, pharmacokinetics and safety were also evaluated.
  
  
  RESULTS
  In total, 315 subjects were randomised. There were no statistically significant differences between treatment groups for the primary efficacy variables. However, analysis of combined data from both trials revealed significant differences favouring DNK333 25 mg over placebo for satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Trends favouring improvement with DNK333 25 mg vs. placebo were seen for all secondary efficacy variables. DNK333 had a safety profile similar to placebo.
  
  
  CONCLUSIONS
  DNK333 25 mg b.d. appears to be effective and well tolerated in women with IBS-D. Further studies with neurokinin antagonists are warranted.
authors.affiliation: Connecticut Gastroenterology Institute, Bristol Hospital, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zakko
authors.forename: G
authors.initials: G
authors.lastname: Barton
authors.forename: E
authors.initials: E
authors.lastname: Weber
authors.forename: C
authors.initials: C
authors.lastname: Dunger-Baldauf
authors.forename: A
authors.initials: A
authors.lastname: Rühl
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001372:Aza Compounds / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001372:Aza Compounds; D001549:Benzamides; C448383:DNK 333; D005765:Gastrointestinal Agents; D010919:Placebos; D018039:Receptors, Tachykinin