title: Eluxadoline for Irritable Bowel Syndrome with Diarrhea.
abstract: Background Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea. Methods We randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial). The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days from weeks 1 through 12 and from weeks 1 through 26. Results For weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) than in the placebo group reached the primary end point (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs. 17.1% with placebo; P=0.01 and P=0.004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs. 16.2%; P<0.001 for both comparisons). For weeks 1 through 26, the corresponding rates in IBS-3001 were 23.4% and 29.3% versus 19.0% (P=0.11 and P<0.001, respectively), and the corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (P=0.001 and P<0.001, respectively). The most common adverse events associated with 75 mg of eluxadoline and 100 mg of eluxadoline, as compared with placebo, were nausea (8.1% and 7.5% vs. 5.1%), constipation (7.4% and 8.6% vs. 2.5%), and abdominal pain (5.8% and 7.2% vs. 4.1%). Pancreatitis developed in 5 (2 in the 75-mg group and 3 in the 100-mg group) of the 1666 patients in the safety population (0.3%). Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women, with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily. (Funded by Furiex Pharmaceuticals, an affiliate of Allergan; IBS-3001 and IBS-3002 ClinicalTrials.gov numbers, NCT01553591 and NCT01553747 , respectively.).
authors.affiliation: From Harvard Medical School, Boston (A.J.L.); Geisel School of Medicine at Dartmouth, Hanover, NH (B.E.L.); Texas Tech University Health Sciences Center, El Paso (M.J.Z.); School of Medicine, Temple University, Philadelphia (R.S.); and Furiex Pharmaceuticals, Morrisville, NC (L.S.D., D.A.A., J.M.D., G.M., R.L., L.T., P.S.C.).
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Lembo
authors.forename: Brian E
authors.initials: BE
authors.lastname: Lacy
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Zuckerman
authors.forename: Ron
authors.initials: R
authors.lastname: Schey
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Dove
authors.forename: David A
authors.initials: DA
authors.lastname: Andrae
authors.forename: J Michael
authors.initials: JM
authors.lastname: Davenport
authors.forename: Gail
authors.initials: G
authors.lastname: McIntyre
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Lisa
authors.initials: L
authors.lastname: Turner
authors.forename: Paul S
authors.initials: PS
authors.lastname: Covington
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D000368:Aged; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced; D010649:Phenylalanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007093:Imidazoles; C583636:eluxadoline; D010649:Phenylalanine