Travelers' Diarrhea
Conditions
Keywords
Travelers, diarrhea, rifaximin, equivalence
Brief summary
This study compared safety and efficacy of a generic rifaximin tablet to the reference listed drug in the treatment of travelers' diarrhea. Additionally both the generic and reference formulations were tested for superiority against a placebo tablet. It was planned that 450 patients would be enrolled, but only 28 patients were randomized. Of these, 1 patient discontinued due to failure to meet the inclusion/exclusion criteria. The remaining 27 patients received study drug and 25 patients completed the study. The study was terminated due to slow enrolment. The final analysis included only safety analysis in the Safety population, due to the low number of randomized patients. No efficacy analysis was performed.
Interventions
DRUGRifaximin (Sandoz GmbH) tablet
200 mg tablet administered orally.
200 mg tablet administered orally
DRUGPlacebo
Matching Placebo tablet administered orally
Sponsors
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is able to read and understood the language of the Informed Consent Form and Patient Information. * International travelers with a duration of stay in host country long enough to attend schedules visits. * Affected by naturally acquired acute diarrhea, defined as the passage of at least 3 unformed stools within 24 hours immediately preceding randomization preceding randomization
Exclusion criteria
* Hypersensitivity to rifaximin or any of the rifamycin antimicrobial agents or to any of the excipients of the study drug. * Pregnant, breast feeding or planning pregnancy * Acute diarrhea for \> 72 hours immediately prior to randomization. * Presence of fever (≥ 100 °F/37.8°C) or hematochezia (blood in stool, noted visually) or clinical findings suggesting moderate or severe dehydration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate | study day 5 +/- 1 day | Clinical cure was defined as either 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 two soft stools passed within a 24 hour period with no fever and no other enteric symptoms except for mild excess gas/flatulence. |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Patients With Clinical Failure | within 5 study days |
| Proportion of Patients With Improvement of Diarrheal Syndrome | within 5 study days |
| Time to Last Unformed Stool | within 5 study days |
| The Presence or Absence and Severity of Signs and Symptoms of Enteric Infection | within 5 study days |
| Microbiological Cure Rate | study day 5 |
| Number of Unformed Stools | within 5 study days |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin Patients received Rifaximin 200 mg tablet 3 times per day for 3 days. | 12 |
| Xifaxan Patients received Xifaxan 200 mg tablet 3 times per day for 3 days. | 11 |
| Placebo Patients received placebo tablet 3 times per day for 3 days. | 4 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not meet inc./exc. criteria | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Rifaximin | Xifaxan | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 36.3 Years STANDARD_DEVIATION 18.27 | 38.2 Years STANDARD_DEVIATION 18.69 | 35.8 Years STANDARD_DEVIATION 21.93 | 37.0 Years STANDARD_DEVIATION 18.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 4 Participants | 26 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 1 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 3 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 4 |
| other Total, other adverse events | 2 / 12 | 5 / 11 | 0 / 4 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 0 / 4 |
Outcome results
Primary
Clinical Cure Rate
Clinical cure was defined as either 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 two soft stools passed within a 24 hour period with no fever and no other enteric symptoms except for mild excess gas/flatulence.
Time frame: study day 5 +/- 1 day
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.
Secondary
Microbiological Cure Rate
Time frame: study day 5
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.
Secondary
Number of Unformed Stools
Time frame: within 5 study days
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.
Secondary
Proportion of Patients With Clinical Failure
Time frame: within 5 study days
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.
Secondary
Proportion of Patients With Improvement of Diarrheal Syndrome
Time frame: within 5 study days
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.
Secondary
The Presence or Absence and Severity of Signs and Symptoms of Enteric Infection
Time frame: within 5 study days
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.
Secondary
Time to Last Unformed Stool
Time frame: within 5 study days
Population: The study was terminated after only 28 patients (6% of planned population) were randomized. In line with the predefined Statistical Analysis Plan (SAP) no efficacy analysis was performed due to low sample size.