title: Randomised clinical trial: exploratory phase 2 study of ONO-2952 in diarrhoea-predominant irritable bowel syndrome.
abstract: ONO-2952 is a novel and selective inhibitor of translocator protein 18 kDa that reduces stress-induced defecation and visceral hyperalgesia in rat models.
  
  
  
  To evaluate the efficacy and safety of ONO-2952 in females with irritable bowel syndrome with diarrhoea in an exploratory proof-of-concept study.
  
  
  
  A randomised, double-blind, placebo-controlled study was conducted at 49 US centres. Two hundred subjects with irritable bowel syndrome with diarrhoea (Rome III criteria) were randomised to ONO-2952 20 mg, or 60 mg, or placebo. Subjects recorded irritable bowel syndrome symptoms daily during a 2-week baseline period, the 4-week treatment period and for 4 weeks post-treatment. The co-primary endpoints were change from baseline to week 4 in abdominal pain, stool consistency and stool frequency.
  
  
  
  Improvements in irritable bowel syndrome symptoms were seen with ONO-2952 over placebo in per-protocol analyses for all three co-primary endpoints, but these did not reach statistical significance at the 5% level. The largest improvement was seen with ONO-2952 60 mg. ONO-2952 was well tolerated with a safety profile similar to that of placebo. Most adverse events were mild or moderate in severity and not treatment related.
  
  
  
  ONO-2952 showed evidence of clinical efficacy in reducing irritable bowel syndrome-related symptoms in female subjects with irritable bowel syndrome with diarrhoea, and further evaluation is, therefore, warranted to assess its potential as a treatment for irritable bowel syndrome with diarrhoea (NCT01844180).
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Whitehead
authors.affiliation: Ono Pharma UK Ltd, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Duffy
authors.affiliation: Ono Pharma UK Ltd, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Sharpe
authors.affiliation: Ono Pharma UK Ltd, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Nabata
authors.affiliation: Ono Pharma UK Ltd, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bruce
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000818:Animals; D003521:Cyclopropanes / Q000627:therapeutic use*; D003967:Diarrhea / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D018079:Receptors, GABA / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D003521:Cyclopropanes; D006576:Heterocyclic Compounds, 4 or More Rings; C000607300:ONO-2952; D018079:Receptors, GABA; C499229:TSPO protein, human