Tags

Type your tag names separated by a space and hit enter

Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study.
Gastroenterology. 2013 Aug; 145(2):329-38.e1.G

Abstract

BACKGROUND & AIMS

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+Show Affiliations

Furiex Pharmaceuticals, Morrisville, North Carolina 27560, USA. scott.dove@furiex.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23583433

Citation

Dove, Leonard S., et al. "Eluxadoline Benefits Patients With Irritable Bowel Syndrome With Diarrhea in a Phase 2 Study." Gastroenterology, vol. 145, no. 2, 2013, pp. 329-38.e1.
Dove LS, Lembo A, Randall CW, et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013;145(2):329-38.e1.
Dove, L. S., Lembo, A., Randall, C. W., Fogel, R., Andrae, D., Davenport, J. M., McIntyre, G., Almenoff, J. S., & Covington, P. S. (2013). Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology, 145(2), 329-e1. https://doi.org/10.1053/j.gastro.2013.04.006
Dove LS, et al. Eluxadoline Benefits Patients With Irritable Bowel Syndrome With Diarrhea in a Phase 2 Study. Gastroenterology. 2013;145(2):329-38.e1. PubMed PMID: 23583433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. AU - Dove,Leonard S, AU - Lembo,Anthony, AU - Randall,Charles W, AU - Fogel,Ronald, AU - Andrae,David, AU - Davenport,J Michael, AU - McIntyre,Gail, AU - Almenoff,June S, AU - Covington,Paul S, Y1 - 2013/04/09/ PY - 2012/10/09/received PY - 2013/04/02/revised PY - 2013/04/04/accepted PY - 2013/4/16/entrez PY - 2013/4/16/pubmed PY - 2013/9/28/medline KW - Clinical Trial KW - DOR KW - Drug KW - EQ-5D KW - EuroQoL-5 Dimension KW - FDA KW - Functional Bowel Disorders KW - GLMM KW - IBS KW - IBS-D KW - IBS-QOL KW - IBS-Quality of Life KW - IBS-SSS KW - IBS-Symptom Severity Score KW - IVRS KW - MOR KW - Transit KW - US Food and Drug Administration KW - WAP KW - generalized linear mixed effects model KW - interactive voice response system KW - irritable bowel syndrome KW - irritable bowel syndrome with diarrhea KW - worst abdominal pain KW - δ opioid receptor KW - μ opioid receptor SP - 329 EP - 38.e1 JF - Gastroenterology JO - Gastroenterology VL - 145 IS - 2 N2 - BACKGROUND & AIMS: 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/23583433/Eluxadoline_benefits_patients_with_irritable_bowel_syndrome_with_diarrhea_in_a_phase_2_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(13)00499-X DB - PRIME DP - Unbound Medicine ER -