Back to resultsStudy Comparing Rifaximin With Xifaxan 200 mg in Traveler's Diarrhea
Primary Purpose
Diarrhea
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rifaximin
Xifaxan®
Placebo Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Diarrhea
Eligibility Criteria
Inclusion Criteria:
- Adult male or nonpregnant female aged ≥18 years non-indigenous travelers (for example; visiting students/faculty or international tourists) affected by naturally acquired acute diarrhea. Diarrhea is defined as the passage of at least 3 unformed stools in a 24-hour period. Stools are classified as formed (retains shape), soft (assumes shape of container), or watery (can be poured). When using this classification, both soft and watery stools are unformed and abnormal.
- At least 3 unformed stools recorded within the 24 hours immediately preceding randomization.
At least 1 of the following signs and symptoms of enteric infection:
- abdominal pain or cramps
- nausea
- vomiting
- fecal urgency
- excessive gas/flatulence
- tenesmus
- Women of child-bearing potential have a negative pregnancy test prior to beginning therapy and agree to use effective contraceptive methods during the study.
Exclusion Criteria:
- Pregnant, breast feeding, or planning a pregnancy.
- Immediately prior to randomization, acute diarrhea for >72 hours.
Presence of:
- fever (≥100 degrees fahrenheit [°F] or ≥37.8 degrees celsius [°C]), or
- hematochezia (blood in stool), or
- clinical findings suggesting moderate or severe dehydration.
- Active, uncontrolled, or clinically significant diseases or disorders of the heart, lung, kidney, gastrointestinal (GI) tract (other than infectious diarrhea in travelers), or central nervous system.
Administration of any of the following:
- any antimicrobial agents with an expected activity against enteric bacterial pathogens within 7 days preceding randomization
- more than 2 doses of a symptomatic antidiarrheal compound such as antimotility agents, absorbent agents, and antisecretory agents within 8 hours preceding randomization
- Use of any drug such as aspirin or ibuprofen (Advil), which can cause GI bleeding. Acetaminophen (Tylenol) or paracetamol is acceptable.
Sites / Locations
- Site 1
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Generic Rifaximin 200 mg Tablets
Xifaxan 200 mg Tablets
Placebo
Arm Description
Participants will receive a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
Participants will receive a xifaxan 200 mg tablet 3 times daily orally for 3 days.
Participants will receive a rifaximin placebo tablet 3 times daily orally for 3 days.
Outcomes
Primary Outcome Measures
Number of Participants Who Achieved Clinical Cure at Test of Cure (TOC) Visit (Within 24 to 72 Hours From the Time of Last Dose): Per-Protocol (PP) Population
Clinical cure was defined as either of the following: No stools or only formed stools within a 48-hour period and no fever, with or without other enteric symptoms or; No watery stools or no more than 2 soft stools passed within a 24-hour period with no fever and no other enteric symptoms except for mild excess gas/flatulence. Bioequivalence evaluation between test (generic rifaximin 200 mg tablets) and reference groups (xifaxan 200 mg tablets) was conducted in this endpoint, hence placebo group was not included. Participants who were discontinued early from the study due to lack of treatment effect after completing 9 doses within 72 hours from the time of first dose were included in the PP population using Last Observation Carried Forward (LOCF) method. Additionally, participants whose condition worsened and who required alternate or supplemental therapy for the treatment of travelers' diarrhea were discontinued and included in the PP population analysis using LOCF.
Number of Participants Who Achieved Clinical Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose): Modified Intent-to-Treat (mITT) Population
Clinical cure was defined as either of the following: No stools or only formed stools within a 48-hour period and no fever, with or without other enteric symptoms or; No watery stools or no more than 2 soft stools passed within a 24-hour period with no fever and no other enteric symptoms except for mild excess gas/flatulence. Participants discontinued early for reasons other than "lack of treatment effect after completing 9 doses within 72 hours from the time of first dose" and for "participants whose condition worsened and who required alternate or supplemental therapy for the treatment of travelers' diarrhea" were included in the mITT population analysis using LOCF.
Secondary Outcome Measures
Time to Last Unformed Stool (TLUS)
TLUS was defined as the interval beginning with the first dose of study drug and ending with the last unformed stool passed within a period of 120 hours (within 48 hours from the time of last dose [at 72 hours]). Mathematically, TLUS was calculated as follows. TLUS (hours) = date/time of last unformed stool within 48 hours from the time of last dose - date/time of first dose.
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Participants were considered to have achieved microbiological cure if the pathogen identified at Day 1 is no longer found in the stool at the TOC visit.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02498418
Brief Title
Study Comparing Rifaximin With Xifaxan 200 mg in Traveler's Diarrhea
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Multicenter, Bioequivalence Study With Clinical Endpoint Comparing Rifaximin 200-mg Tablets With Xifaxan® 200-mg Tablets in the Treatment of Travelers' Diarrhea
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
January 6, 2016 (Actual)
Primary Completion Date
February 28, 2017 (Actual)
Study Completion Date
February 28, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actavis Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective is to demonstrate rifaximin 200 milligrams (mg) tablets (test) and Xifaxan® 200 mg tablets (reference) are clinically bioequivalent with respect to the clinical cure rates when administered 3 times a day (TID) for 3 days in participants with travelers' diarrhea.
Detailed Description
This is a randomized, placebo-controlled bioequivalent study with a clinical endpoint in the treatment of travelers' diarrhea. After 3 unformed stools are recorded within the 24 hours immediately preceding randomization, participants are to be randomized to receive the generic rifaximin 200 mg oral tablet, Xifaxan (the reference listed drug)200 mg oral tablet, or placebo 3 times daily for 3 days (that is; on Days 1, 2, and 3).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diarrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
739 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Generic Rifaximin 200 mg Tablets
Arm Type
Experimental
Arm Description
Participants will receive a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
Arm Title
Xifaxan 200 mg Tablets
Arm Type
Active Comparator
Arm Description
Participants will receive a xifaxan 200 mg tablet 3 times daily orally for 3 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive a rifaximin placebo tablet 3 times daily orally for 3 days.
Intervention Type
Drug
Intervention Name(s)
Rifaximin
Intervention Description
Tablets, generic formulation of the brand product.
Intervention Type
Drug
Intervention Name(s)
Xifaxan®
Intervention Description
Tablets, brand product.
Intervention Type
Drug
Intervention Name(s)
Placebo Tablet
Intervention Description
Placebo tablets in the same image of the generic rifaximin. Has no active ingredient.
Primary Outcome Measure Information:
Title
Number of Participants Who Achieved Clinical Cure at Test of Cure (TOC) Visit (Within 24 to 72 Hours From the Time of Last Dose): Per-Protocol (PP) Population
Description
Clinical cure was defined as either of the following: No stools or only formed stools within a 48-hour period and no fever, with or without other enteric symptoms or; No watery stools or no more than 2 soft stools passed within a 24-hour period with no fever and no other enteric symptoms except for mild excess gas/flatulence. Bioequivalence evaluation between test (generic rifaximin 200 mg tablets) and reference groups (xifaxan 200 mg tablets) was conducted in this endpoint, hence placebo group was not included. Participants who were discontinued early from the study due to lack of treatment effect after completing 9 doses within 72 hours from the time of first dose were included in the PP population using Last Observation Carried Forward (LOCF) method. Additionally, participants whose condition worsened and who required alternate or supplemental therapy for the treatment of travelers' diarrhea were discontinued and included in the PP population analysis using LOCF.
Time Frame
TOC visit (Day 5, 6 or 7)
Title
Number of Participants Who Achieved Clinical Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose): Modified Intent-to-Treat (mITT) Population
Description
Clinical cure was defined as either of the following: No stools or only formed stools within a 48-hour period and no fever, with or without other enteric symptoms or; No watery stools or no more than 2 soft stools passed within a 24-hour period with no fever and no other enteric symptoms except for mild excess gas/flatulence. Participants discontinued early for reasons other than "lack of treatment effect after completing 9 doses within 72 hours from the time of first dose" and for "participants whose condition worsened and who required alternate or supplemental therapy for the treatment of travelers' diarrhea" were included in the mITT population analysis using LOCF.
Time Frame
TOC visit (Day 5, 6 ,or 7)
Secondary Outcome Measure Information:
Title
Time to Last Unformed Stool (TLUS)
Description
TLUS was defined as the interval beginning with the first dose of study drug and ending with the last unformed stool passed within a period of 120 hours (within 48 hours from the time of last dose [at 72 hours]). Mathematically, TLUS was calculated as follows. TLUS (hours) = date/time of last unformed stool within 48 hours from the time of last dose - date/time of first dose.
Time Frame
Day 1 to Day 5
Title
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Description
Participants were considered to have achieved microbiological cure if the pathogen identified at Day 1 is no longer found in the stool at the TOC visit.
Time Frame
TOC visit (Day 5, 6, or 7)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or nonpregnant female aged ≥18 years non-indigenous travelers (for example; visiting students/faculty or international tourists) affected by naturally acquired acute diarrhea. Diarrhea is defined as the passage of at least 3 unformed stools in a 24-hour period. Stools are classified as formed (retains shape), soft (assumes shape of container), or watery (can be poured). When using this classification, both soft and watery stools are unformed and abnormal.
At least 3 unformed stools recorded within the 24 hours immediately preceding randomization.
At least 1 of the following signs and symptoms of enteric infection:
abdominal pain or cramps
nausea
vomiting
fecal urgency
excessive gas/flatulence
tenesmus
Women of child-bearing potential have a negative pregnancy test prior to beginning therapy and agree to use effective contraceptive methods during the study.
Exclusion Criteria:
Pregnant, breast feeding, or planning a pregnancy.
Immediately prior to randomization, acute diarrhea for >72 hours.
Presence of:
fever (≥100 degrees fahrenheit [°F] or ≥37.8 degrees celsius [°C]), or
hematochezia (blood in stool), or
clinical findings suggesting moderate or severe dehydration.
Active, uncontrolled, or clinically significant diseases or disorders of the heart, lung, kidney, gastrointestinal (GI) tract (other than infectious diarrhea in travelers), or central nervous system.
Administration of any of the following:
any antimicrobial agents with an expected activity against enteric bacterial pathogens within 7 days preceding randomization
more than 2 doses of a symptomatic antidiarrheal compound such as antimotility agents, absorbent agents, and antisecretory agents within 8 hours preceding randomization
Use of any drug such as aspirin or ibuprofen (Advil), which can cause GI bleeding. Acetaminophen (Tylenol) or paracetamol is acceptable.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Actavis Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Site 1
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33134
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Study Comparing Rifaximin With Xifaxan 200 mg in Traveler's Diarrhea
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