Irritable Bowel Syndrome With Diarrhea (IBS-D) Rifaximin Re-Treatment Study

Phase 3

Completed

Conditions: Irritable Bowel Syndrome With Diarrhea

Interventions: Drug: open-label rifaximin
Drug: double-blind rifaximin
Drug: double-blind placebo

Registration Number: NCT01543178

Lead Sponsor: Bausch Health Americas, Inc.

Brief Summary: This study will evaluate the effectiveness and safety of repeat treatment with rifaximin 550 mg three times a day in patients with IBS with diarrhea who respond to initial treatment of rifaximin 550 mg three times a day.

Detailed Description: It is important in chronic conditions to have information about how a product that is intended for short course administration in order to confer prolonged benefit should be administered beyond the first cycle of use once symptoms reappear. This Phase 3 study will evaluate the efficacy and safety of repeat treatment with rifaximin 550 mg three times daily (TID) for 14 days in subjects with IBS-D who respond to an initial treatment course with rifaximin 550 mg TID for 14 days.

This study consists of several treatment phases outlined below:

Screening/Treatment 1 Phase. Subjects will receive single-blind placebo TID for 7-13 days and answer daily IBS symptom-related questions.

Treatment 2 Phase. Eligible subjects will receive open-label rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up. Responders will continue into Maintenance Phase 1. Nonresponders will withdraw from the study.

Maintenance Phase 1. Subjects will continue the treatment-free follow-up period for up to 18 weeks until either: 1) they experience recurrence or 2) enrollment is met in the Treatment 3 Phase (Double Blind Repeat Treatment Phase). Subjects who do not meet recurrence criteria by the end of the Maintenance Phase 1 will withdraw from the study.

Treatment 3 Phase/ Double Blind Repeat Treatment Phase. Subjects who meet criteria for recurrence will be randomized 1:1 to receive either rifaximin 550 mg TID or placebo TID for 2 weeks with a 4-week treatment-free follow-up.

Primary efficacy analysis will be performed at the end of the Treatment 3 Phase (at Week 6 of the double-blind period).

Maintenance Phase 2. All subjects continued into an additional treatment-free follow-up period of up to 6 weeks (Maintenance Phase 2).

Treatment 4 Phase/Second Repeat Treatment Phase. Subjects will receive the same double-blind treatment as previously assigned in the Treatment 3 Phase for 2 weeks with a 4-week treatment-free follow-up.

A lactulose breath test sub-study will be conducted at select sites.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2583

Inclusion Criteria

IBS confirmed by Rome III diagnostic criteria.
At least 18 years of age.
Colonoscopy within the past 10 years to rule out inflammatory bowel disease; or flexible sigmoidoscopy if < 50 years of age or previous colonoscopy > 10 years prior.
Willing to maintain a stable diet. including vitamins, supplements, and nutraceuticals.

Exclusion Criteria

Diabetes (Type 1 or 2).
Lactose intolerance and not controlled by a lactose-free diet.
Pregnant or planning to become pregnant or is lactating.
History of HIV or hepatitis B or C.
Participation in investigational study within past 30 days.
Taking rifaximin or any other antibiotic within past 60 days.
Unstable cardiovascular or pulmonary disease, with change in treatment in last 30 days due to worsening disease condition.
History of GI surgery.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rifaximin open-label	open-label rifaximin	Subjects will receive open-label rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up. Responders will continue into Maintenance Phase 1 (treatment free). Nonresponders will withdraw from the study. Subjects who meet criteria for recurrence in Maintenance Phase 1 enter the double-blind period and are randomized 1:1 to receive rifaximin 550 mg or placebo.
Double-blind rifaximin (retreatment)	open-label rifaximin	Subjects in this arm receive rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up.
Double-blind rifaximin (retreatment)	double-blind rifaximin	Subjects in this arm receive rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up.
Double-blind placebo (retreatment)	double-blind placebo	Subjects in this arm receive placebo TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with placebo TID for 2 weeks with a 4-week treatment-free follow-up.
Double-blind placebo (retreatment)	open-label rifaximin	Subjects in this arm receive placebo TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with placebo TID for 2 weeks with a 4-week treatment-free follow-up.

Primary Outcome Measures

Name	Time	Method
Repeat Treatment Responders	4-week treatment-free follow-up in double-blind repeat treatment phase.	Subjects who respond to repeat treatment in both IBS-related abdominal pain and stool consistency. The proportion of patients who responded to repeat treatment during the first double-blind repeat treatment phase is presented. Response is defined as improvement from baseline in abdominal pain AND reduction from baseline in diarrhea.

Secondary Outcome Measures