A Phase II, multicentric, randomized, double-blind, placebo controlled, proof of concept study of efficacy and safety of Rifamycin SV-MMX® 600 mg tablets administered three or two times daily to patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

Abstract

Background: Treatment with non-resorbable antibiotics is effective in diarrhea predominant irritable bowel syndrome (IBS-D). Multimatrix® (MMX®) formulations ensure targeted drug delivery to the mid-distal small bowel and colon - traditionally considered the origin of IBS symptoms.

Aim: To assess the efficacy of Rifamycin SV-MMX for the treatment of IBS-D.

Methods: Randomized controlled trial in IBS-D patients (Rome IV). Patients received Rifamycin SV-MMX® 600 mg (b.i.d = 1200mg/day or t.i.d =1800mg/day) or placebo for 2 weeks. Primary endpoint was responder rate in the first treatment week on the full analysis set (FAS). Response was defined as decrease in average abdominal pain ≥ 30% AND ≥50% reduction of days with stool type 6 or 7 based on daily reporting.

Results: 279 patients were randomized (= ITT), 264 of were included in the FAS. More patients with Rifamycin SV-MMX® b.i.d (22/88, 25.00%) met the primary endpoint than t.i.d (10/81, 12.35%) or placebo (9/95, 9.47%) in both FAS and ITT. Adjusted Odds ratio (AOR) for b.i.d. vs placebo was 3.26 (95% CI: 1.39-7.67; p=0.007) and for t.i.d. vs b.i.d. 0.40 (95% CI: 0.17-0.92; p=0.031). Following treatment, the percentage of monthly global responders was higher in the b.i.d. group vs placebo in the first month (64.2% vs 46.6 %, AOR= 2.14 95% CI: 1.15; 4.00; p=0.0173) and first 2 months.

Conclusion: Rifamycin SV-MMX® 600mg b.i.d. was more effective than placebo and t.i.d. dosing in the first week of treatment. Two months following treatment, Rifamycin SV-MMX® 600mg b.i.d. provided more global symptom relief than placebo.