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.

Abstract

Introduction: Treatment with nonresorbable 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. To assess the efficacy of rifamycin SV-MMX for the treatment of IBS-D.

Methods: Randomized controlled trial in patients with IBS-D (Rome IV). Patients received rifamycin SV-MMX 600 mg (b.i.d = 1200 mg/d or t.i.d = 1800 mg/d) or placebo for 2 weeks. Primary end point 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: A total of 279 patients were randomized (=ITT), and 264 of were included in the FAS. More patients with rifamycin SV-MMX b.i.d (22/88, 25.00%) met the primary end point 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% confidence interval (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). After 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%, adjusted odds ratio = 2.14 95% CI: 1.15; 4.00; P = 0.0173) and first 2 months.

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