title: Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study.
abstract: OBJECTIVE
  Simultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, μ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D.
  
  
  METHODS
  We randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks. The primary end point was clinical response at week 4, defined by a mean reduction in daily pain score from baseline of ≥ 30%, and of at least 2 points on 0-10 scale, as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale (1-7) for at least 66% of daily diary entries during that week.
  
  
  RESULTS
  Significantly more patients receiving 25 mg (12.0%) or 200 mg (13.8%) eluxadoline met the primary end point of clinical response than patients given placebo (5.7%; P < .05). Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments (P < .05). Additionally, patients receiving 100 mg (28.0%) or 200 mg (28.5%) eluxadoline were significantly more likely than those receiving placebo (13.8%; P < .005) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study. Eluxadoline was well tolerated with a low incidence of constipation.
  
  
  CONCLUSIONS
  In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D.
authors.affiliation: Furiex Pharmaceuticals, Morrisville, North Carolina 27560, USA. scott.dove@furiex.com
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Dove
authors.forename: Anthony
authors.initials: A
authors.lastname: Lembo
authors.forename: Charles W
authors.initials: CW
authors.lastname: Randall
authors.forename: Ronald
authors.initials: R
authors.lastname: Fogel
authors.forename: David
authors.initials: D
authors.lastname: Andrae
authors.forename: J Michael
authors.initials: JM
authors.lastname: Davenport
authors.forename: Gail
authors.initials: G
authors.lastname: McIntyre
authors.forename: June S
authors.initials: JS
authors.lastname: Almenoff
authors.forename: Paul S
authors.initials: PS
authors.lastname: Covington
mesh_terms: D000328:Adult; D003967:Diarrhea / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D007093:Imidazoles; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C583636:eluxadoline; D010649:Phenylalanine
keywords: Clinical Trial; DOR; Drug; EQ-5D; EuroQoL-5 Dimension; FDA; Functional Bowel Disorders; GLMM; IBS; IBS-D; IBS-QOL; IBS-Quality of Life; IBS-SSS; IBS-Symptom Severity Score; IVRS; MOR; Transit; US Food and Drug Administration; WAP; generalized linear mixed effects model; interactive voice response system; irritable bowel syndrome; irritable bowel syndrome with diarrhea; worst abdominal pain; δ opioid receptor; μ opioid receptor