A Study Comparing Two Rifaximin Tablets in Patients With Travelers' Diarrhea.

• Sponsor: Sandoz (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02920242
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 3
• Actual Duration (Months): 5.2
• Patients Per Site Per Month: 5.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Travelers' Diarrhea	Drug: Rifaximin (Sandoz GmbH) tablet; Drug: Rifaximin (Xifaxan); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Parallel Group, Placebo-controlled, Multi-center, Therapeutic Equivalence Study to Compare Rifaximin 200 mg Tablets (Sandoz GmbH) to Xifaxan® 200 mg Tablets (Salix Pharmaceuticals, Inc.) and Placebo in Patients With Travelers' Diarrhea
• Actual Study Start Date: Dec 15, 2016
• Actual Primary Completion Date: May 23, 2017
• Actual Study Completion Date: May 23, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rifaximin Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Drug: Rifaximin (Sandoz GmbH) tablet; 200 mg tablet administered orally.
Active Comparator: Xifaxan Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Drug: Rifaximin (Xifaxan); 200 mg tablet administered orally; Other Names: Xifaxan®
Placebo Comparator: Placebo Patients received placebo tablet 3 times per day for 3 days.	Drug: Placebo; Matching Placebo tablet administered orally

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Time to Last Unformed Stool [within 5 study days]

2. Proportion of Patients With Clinical Failure [within 5 study days]

3. Proportion of Patients With Improvement of Diarrheal Syndrome [within 5 study days]

4. Number of Unformed Stools [within 5 study days]

5. The Presence or Absence and Severity of Signs and Symptoms of Enteric Infection [within 5 study days]

6. Microbiological Cure Rate [study day 5]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sandoz Investigative Site	Mexico City		Mexico

Sponsors and Collaborators

• Sandoz

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 29, 2015
• Statistical Analysis Plan - May 26, 2017

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT02920242
• Other Study ID Numbers: 1526 RIF_2
• First Posted: Sep 30, 2016
• Last Update Posted: Mar 25, 2019
• Last Verified: Dec 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sandoz: Travelers; diarrhea; rifaximin; equivalence
• Additional relevant MeSH terms: Dysentery; Diarrhea; Rifaximin

Study Results

Participant Flow

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Period Title: Overall Study
STARTED	13	11	4
Safety Set	12	11	4
COMPLETED	11	11	3
NOT COMPLETED	2	0	1

Baseline Characteristics

Arm/Group Title	Rifaximin	Xifaxan	Placebo	Total
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.	Total of all reporting groups
Overall Participants	12	11	4	27
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.3 (18.27)	38.2 (18.69)	35.8 (21.93)	37.0 (18.22)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	7 63.6%	1 25%	13 48.1%
Male	7 58.3%	4 36.4%	3 75%	14 51.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 8.3%	0 0%	0 0%	1 3.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	11 91.7%	11 100%	4 100%	26 96.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure Rate
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

2. Secondary Outcome

Title	Time to Last Unformed Stool
Time Frame	within 5 study days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

3. Secondary Outcome

Title	Proportion of Patients With Clinical Failure
Time Frame	within 5 study days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

4. Secondary Outcome

Title	Proportion of Patients With Improvement of Diarrheal Syndrome
Time Frame	within 5 study days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

5. Secondary Outcome

Title	Number of Unformed Stools
Time Frame	within 5 study days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

6. Secondary Outcome

Title	The Presence or Absence and Severity of Signs and Symptoms of Enteric Infection
Time Frame	within 5 study days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

7. Secondary Outcome

Title	Microbiological Cure Rate
Time Frame	study day 5

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Xifaxan	Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.	Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.	Patients received placebo tablet 3 times per day for 3 days.
Measure Participants	0	0	0

Adverse Events

Time Frame	up to day 5 +/- 1 day
Arm/Group Title	Rifaximin		Xifaxan		Placebo
Arm/Group Description	Patients received Rifaximin 200 mg tablet 3 times per day for 3 days.		Patients received Xifaxan 200 mg tablet 3 times per day for 3 days.		Patients received placebo tablet 3 times per day for 3 days.
All Cause Mortality
	Rifaximin		Xifaxan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)		0/4 (0%)
Serious Adverse Events
	Rifaximin		Xifaxan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Rifaximin		Xifaxan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		5/11 (45.5%)		0/4 (0%)
Eye disorders
Lacrimation increased	0/12 (0%)		1/11 (9.1%)		0/4 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/12 (0%)		1/11 (9.1%)		0/4 (0%)
Constipation	1/12 (8.3%)		0/11 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Medication error	0/12 (0%)		1/11 (9.1%)		0/4 (0%)
Nervous system disorders
Dizziness	0/12 (0%)		2/11 (18.2%)		0/4 (0%)
Headache	1/12 (8.3%)		3/11 (27.3%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.