Patients with Diarrhea-predominant Irritable Bowel Syndrome Experience Symptom Relief with Eluxadoline

The authors of “Eluxadoline Benefits Patients with Irritable Bowel Syndrome with Diarrhea in a Phase 2 Study,” published in Gastroenterology, evaluated the safety and efficacy of the μ-opioid receptor agonist and δ-opioid receptor antagonist eluxadoline in patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

For the study, researchers randomized 807 patients with IBS-D to receive twice-daily oral placebo or 5 mg, 25 mg, 100 mg, or 200 mg oral eluxadoline for 12 weeks. Patients were evaluated at 2, 4, 8, 12, 14 weeks and recorded symptoms in a daily diary.

The primary endpoints of the study were:

• Clinical response defined by a mean reduction of 30% or greater in daily pain score from baseline, measured at week 4
• Reduction of at least 2 points on a 0−10 scale
• Stool consistency score of 3 or 4 on the Bristol Stool Scale for at least two-thirds of daily diary entries during that week

The authors reported that more patients treated with 25 mg (12.0%) or 200 mg (13.8%) eluxadoline experienced clinical response at week 4 compared to patients who received placebo (5.7%). They also reported that more patients who received 100 mg or 200 mg eluxadoline had “greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments.”

According to this report on the study, patients who received treatment with 100 mg eluxadoline “experienced improved global symptom relief at weeks 8 and 12 (P<.001 for both) and greater symptom improvement as indicated by IBS-Symptom Severity Score at 4, 8 and 12 weeks (P=.011 at 4 weeks; P<.001 at 8 and 12 weeks). IBS-Quality-of-Life scores also were significantly improved compared with placebo at 4 (P=.012), 8 and 12 weeks (P<.001 for both).”

Patients treated with 200 mg eluxadoline experienced similar results, but with a higher incidence of severe adverse events such as abdominal pain, constipation, nausea, and vomiting.

Based on these results, the authors concluded that 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.”

In related news, Furiex Pharmaceuticals, Inc. recently announced it had completed patient enrollment in two phase III clinical trials studying eluxadoline for the treatment of IBS-D. According to the announcement, one study “has a 52-week treatment period and the other a 30-week treatment period. Each study has three treatment arms, placebo, 75 mg eluxadoline twice a day and 100 mg eluxadoline twice a day, with approximately 375 patients per arm, and is designed to capture both the U.S. Food and Drug Administration and the European Medicines Agency endpoints for treatment of IBS-D.”