Patients with IBS-D in two phase II trials of eluxadoline experienced sustained improvements in abdominal pain and bowel symptoms at 26 weeks of treatment, with mild side effects.
Eluxadoline, a locally active, mixed mu opioid receptor (µOR) agonist and delta opioid receptor (δOR) antagonist being developed to treat diarrhea-predominant irritable bowel syndrome IBS-D) has shown success in two phase 3 clinical trials.
Two double-blind, placebo-controlled, trials (IBS3001 and IBS3002) randomized patients meeting Rome III criteria for IBS-D to treatment with eluxadoline (75 mg or 100 mg twice daily) or placebo. Both trials assessed efficacy through 26 weeks. Thereafter, IBS3001 included an additional 26 weeks of double-blind treatment for long-term safety evaluations while IBS3002 included a 4-week placebo withdrawal phase.
Anthony J. Lembo, MD, Harvard Medical School, Center for Clinical and Translational Research in Gastrointestinal Motility, and Beth Israel Deaconess Medical Center, Division of Gastroenterology, in Boston, MA, presented results Tuesday at DigestiveDisease Week 2014 in Chicago, IL.
Eluxadoline met the primary objectives of composite response with simultaneous improvements in stool consistency and abdominal pain. Study results showed that responder rates of eluxadoline (75mg and 100 mg) were better than placebo in both the studies at 12 weeks and 26 weeks.
Additional efficacy measures included assessments of abdominal and bowel symptoms and global endpoints (eg, adequate relief, IBS-D global symptoms, and quality of life).
Patients receiving eluxadoline at both doses also had greater improvements in numbers of daily bowel movements and urgent episodes, daily IBS-D global symptom scores, and IBS-Quality of Life scores (P<.05).
The most commonadverse events in the two clinical trials were constipation (7.4% and 8.3% for eluxadoline 75 mg and 100 mg; 2.4% for placebo) and nausea (7.8% and 7.3% for eluxadoline 75 mg and 100 mg; 4.8% for placebo). Only 1.3% of patients withdrew from the study due to constipation, Lembo said.
A total of 2,428 patients with IBS-D were enrolled across the two trials (66% females; mean age of 45 years). Enrollees had to have a worst abdominal pain score of at least 3 on a 0-10 scale and a global symptoms score of at least 2 on a 0-4 scale.
Diarrhea-predominant irritable bowel syndrome affects approximately 28 million patients in the United States and Europe. Because of its chronic, relapsing nature, IBS-D is linked with work absenteeism, high medical costs, and poor quality of life.
Lembo said effects of Eluxadoline were seen in the first few days of therapy and were durable throughout the 26 weeks. The treatment was effective in both men and women.
He acknowledged that the success of the trials was modest, with just 10% improvement overall compared with placebo, but added, “The 10% delta over placebo is not dissimilar to other drugs in this class.”