Trial Outcomes & Findings for Study Comparing Rifaximin With Xifaxan 200 mg in Traveler's Diarrhea (NCT NCT02498418)
NCT ID: NCT02498418
Last Updated: 2019-12-05
Results Overview
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.
COMPLETED
PHASE3
739 participants
TOC visit (Day 5, 6 or 7)
2019-12-05
Participant Flow
A total of 739 nonindigenous travelers with naturally acquired acute diarrhea were enrolled and randomized in this study.
Participant milestones
| Measure |
Generic Rifaximin 200 mg Tablets
Participants received a generic rifaximin 200 milligrams (mg) tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
247
|
248
|
244
|
|
Overall Study
Safety Population
|
246
|
247
|
244
|
|
Overall Study
Modified Intent-to-treat Population
|
183
|
186
|
180
|
|
Overall Study
Per-protocol Analysis Set
|
182
|
181
|
176
|
|
Overall Study
COMPLETED
|
245
|
246
|
238
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
6
|
Reasons for withdrawal
| Measure |
Generic Rifaximin 200 mg Tablets
Participants received a generic rifaximin 200 milligrams (mg) tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
1
|
|
Overall Study
Participant taken prohibited medication
|
0
|
1
|
1
|
Baseline Characteristics
Study Comparing Rifaximin With Xifaxan 200 mg in Traveler's Diarrhea
Baseline characteristics by cohort
| Measure |
Generic Rifaximin 200 mg Tablets
n=247 Participants
Participants received a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
n=248 Participants
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
n=244 Participants
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
Total
n=739 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 15.78 • n=5 Participants
|
44.3 years
STANDARD_DEVIATION 16.58 • n=7 Participants
|
42.0 years
STANDARD_DEVIATION 15.21 • n=5 Participants
|
42.9 years
STANDARD_DEVIATION 15.87 • n=4 Participants
|
|
Sex: Female, Male
Female
|
123 Participants
n=5 Participants
|
130 Participants
n=7 Participants
|
132 Participants
n=5 Participants
|
385 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
124 Participants
n=5 Participants
|
118 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
354 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
189 Participants
n=5 Participants
|
188 Participants
n=7 Participants
|
188 Participants
n=5 Participants
|
565 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
58 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
170 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
23 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
208 Participants
n=5 Participants
|
222 Participants
n=7 Participants
|
220 Participants
n=5 Participants
|
650 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
13 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: TOC visit (Day 5, 6 or 7)Population: PP population: randomized participants, met inclusion/exclusion criteria, took 3 days of study drug, were compliant with study drug dose, and completed Visit 3 within 24-72 hours from the time of last dose, with no major protocol deviations/violations that would affect treatment evaluation. LOCF method was used as applicable for this 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.
Outcome measures
| Measure |
Generic Rifaximin 200 mg Tablets
n=182 Participants
Participants received a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
n=181 Participants
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
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
|
90 Participants
|
93 Participants
|
—
|
PRIMARY outcome
Timeframe: TOC visit (Day 5, 6 ,or 7)Population: mITT population included all randomized participants who met all inclusion and none of the exclusion criteria, received at least 1 dose of study drug and provided efficacy and safety data after 1 dose of study drug. LOCF method was used as applicable for this 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.
Outcome measures
| Measure |
Generic Rifaximin 200 mg Tablets
n=183 Participants
Participants received a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
n=186 Participants
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
n=180 Participants
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
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
|
91 Participants
|
95 Participants
|
86 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 5Population: mITT population included all randomized participants who met all inclusion and none of the exclusion criteria, received at least 1 dose of study drug and provided efficacy and safety data after 1 dose of study drug. Here, 'Overall number of participants analyzed'=participants with TLUS in the mITT population.
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.
Outcome measures
| Measure |
Generic Rifaximin 200 mg Tablets
n=182 Participants
Participants received a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
n=186 Participants
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
n=178 Participants
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
Time to Last Unformed Stool (TLUS)
|
65.25 hours
Interval 3.93 to 119.42
|
65.75 hours
Interval 14.1 to 117.08
|
67.01 hours
Interval 16.65 to 117.87
|
SECONDARY outcome
Timeframe: TOC visit (Day 5, 6, or 7)Population: mITT population: all randomized participants who met all inclusion and none of the exclusion criteria, received at least 1 dose of study drug and provided efficacy and safety data after 1 dose. 'Overall number of participants analyzed'=participants evaluable for this endpoint. 'Number analyzed'=participants evaluable for the specified categories.
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.
Outcome measures
| Measure |
Generic Rifaximin 200 mg Tablets
n=51 Participants
Participants received a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
n=47 Participants
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
n=46 Participants
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Enterotoxigenic Escherichia coli (ETEC)
|
43.5 percentage of participants
|
54.5 percentage of participants
|
68.4 percentage of participants
|
|
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Escherichia coli
|
25.5 percentage of participants
|
31.9 percentage of participants
|
17.4 percentage of participants
|
|
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Enteroaggregative Escherichia coli (EAEC)
|
32.0 percentage of participants
|
27.3 percentage of participants
|
26.1 percentage of participants
|
|
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Other microorganisms
|
70.6 percentage of participants
|
81.8 percentage of participants
|
92.9 percentage of participants
|
|
Percentage of Participants Who Achieved Microbiological Cure at TOC Visit (Within 24 to 72 Hours From the Time of Last Dose)
Stool microscopy for ova and parasites
|
83.3 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
Adverse Events
Generic Rifaximin 200 mg Tablets
Xifaxan 200 mg Tablets
Rifaximin Placebo Tablets
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Generic Rifaximin 200 mg Tablets
n=246 participants at risk
Participants received a generic rifaximin 200 mg tablet 3 times daily orally for 3 days.
|
Xifaxan 200 mg Tablets
n=247 participants at risk
Participants received a xifaxan 200 mg tablet 3 times daily orally for 3 days.
|
Rifaximin Placebo Tablets
n=244 participants at risk
Participants received a rifaximin placebo tablet 3 times daily orally for 3 days.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphocytosis
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.41%
1/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
3/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.2%
3/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.41%
1/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.41%
1/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.41%
1/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Defecation urgency
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.82%
2/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Dry mouth
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.41%
1/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Flatulence
|
1.6%
4/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.2%
3/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.6%
4/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.2%
3/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.2%
3/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Rectal tenesmus
|
1.2%
3/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.6%
4/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
3.3%
8/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.41%
1/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Immune system disorders
Food allergy
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Investigations
Blood bilirubin increased
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Investigations
Protein urine present
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Investigations
Urine leukocyte esterase
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Investigations
Weight decreased
|
0.00%
0/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Investigations
White blood cells urine positive
|
0.41%
1/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.40%
1/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
0.81%
2/246 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
0.81%
2/247 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
1.2%
3/244 • Day 1 up to Day 7
Safety population included all randomized participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed.
- Publication restrictions are in place
Restriction type: OTHER