Clinical trial NCT01543178: Irritable Bowel Syndrome With Diarrhea (IBS-D) Rifaximin Re-Treatment Study
Official title: A Study to Assess Repeat Treatment Efficacy and Safety of Rifaximin 550 mg TID in Subjects With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Irritable Bowel Syndrome With Diarrhea
Keywords: IBS
IBS-D
IBS with diarrhea
Diarrhea
Irritable bowel syndrome with diarrhea
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-02
Enrollment: 2583
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Repeat Treatment Responders
timeFrame: 4-week treatment-free follow-up in double-blind repeat treatment phase.
Secondary outcomes:
Other outcomes:
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state: Oklahoma
city: Oklahoma City
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city: Oklahoma City
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state: Pennsylvania
city: Pittsburgh
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state: Pennsylvania
city: Reading
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city: Warwick
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state: Rhode Island
city: Charleston
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state: South Carolina
city: Charleston
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state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Fort Mill
country: United States
state: South Carolina
city: Gaffney
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Brentwood
country: United States
state: Tennessee
city: Bristol
country: United States
state: Tennessee
city: Chattanooga
country: United States
state: Tennessee
city: Franklin
country: United States
state: Tennessee
city: Germantown
country: United States
state: Tennessee
city: Hermitage
country: United States
state: Tennessee
city: Kingsport
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Corsicana
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: Pasadena
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sealy
country: United States
state: Texas
city: Southlake
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Ogden
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Chesapeake
country: United States
state: Virginia
city: Danville
country: United States
state: Virginia
city: Fairfax
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
city: Bellevue
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Manchester
country: United Kingdom
Study officials:
affiliation: Bausch Health Americas, Inc.
name: Enoch Bortey, PhD
role: STUDY_DIRECTOR
References:
citation: Fodor AA, Pimentel M, Chey WD, Lembo A, Golden PL, Israel RJ, Carroll IM. Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome. Gut Microbes. 2019;10(1):22-33. doi: 10.1080/19490976.2018.1460013. Epub 2018 Jul 18.
citation: Cash BD, Pimentel M, Rao SSC, Weinstock L, Chang L, Heimanson Z, Lembo A. Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial. Therap Adv Gastroenterol. 2017 Sep;10(9):689-699. doi: 10.1177/1756283X17726087. Epub 2017 Sep 11.
citation: Pimentel M, Cash BD, Lembo A, Wolf RA, Israel RJ, Schoenfeld P. Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity. Dig Dis Sci. 2017 Sep;62(9):2455-2463. doi: 10.1007/s10620-017-4598-7. Epub 2017 Jun 6.
citation: DuPont HL, Wolf RA, Israel RJ, Pimentel M. Antimicrobial Susceptibility of Staphylococcus Isolates from the Skin of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Treated with Repeat Courses of Rifaximin. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e02165-16. doi: 10.1128/AAC.02165-16. Print 2017 Jan. No abstract available.
citation: Lembo A, Pimentel M, Rao SS, Schoenfeld P, Cash B, Weinstock LB, Paterson C, Bortey E, Forbes WP. Repeat Treatment With Rifaximin Is Safe and Effective in Patients With Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterology. 2016 Dec;151(6):1113-1121. doi: 10.1053/j.gastro.2016.08.003. Epub 2016 Aug 13.