Study to Evaluate Safety and Efficacy of Rifamycin SV MMX in Treating Traveler's Diarrhea in Children Age 12 to 17 Years

Study Overview
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Brief Summary
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This will be a double blind comparative study, performed in pediatric subjects (Age 12-17) traveling to developing regions with a known high incidence of traveler's diarrhea. The subjects will be suffering from acute diarrhea for at least 12 hours, without symptoms of systemic infection.

Detailed Description
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Approximately 142 subjects are expected to be enrolled in the study, 1:1 in the Rifamycin SV MultiMatrix (MMX) plus Oral RehydrationTherapy (ORT) group and in the placebo tablets plus ORT group respectively. The day of randomization (Visit 1, Day 1), the subjects will start the treatment receiving ORT plus Rifamycin SV MMX 400 mg (as two tablets of 200 mg each) twice daily (morning and evening) or ORT plus placebo tablets (as two tablets) twice daily (morning and evening). The subjects will begin the treatment within 72 hours of onset of diarrhea. Treatment duration will last 72 hours. The total number of tablets for the entire treatment course will be 12 (4 × 200 mg tablets/day for 3 days). The administration of the ORT will follow the specification reported in the product label. The tablets will be orally administered during the day. No tablet administration will be done during the night. After enrollment, subjects/their parents/or guardians will complete Diary Cards (PDC) in which will be daily recorded date, time of first tablets intake, time and consistency of each stool, presence of blood in stools, abdominal pain/cramps, flatulence, tenesmus, urgency, nausea, vomiting, fever, adverse events (AEs), and concomitant medications. During the study, the subjects will be assessed for safety and efficacy at Visit 2 (Day 2) and Visit 3 (Day 4/5) as final Study Visit. Stool samples for microbiological assessment will be collected at Visits 1 and 3. Stool will be examined and cultured at local labs for main enteropathogens and for the presence of protozoa, ova and yeasts. Stool samples will be required in a subset population of the Rifamycin SV MMX group, at the Follow-up visit to determine rifamycin concentration in the feces. Blood and urine sampling for routine safety analyses will be collected at Visit 1 and at Visit 3.

Official Title
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Double Blind Study to Evaluate the Safety and Efficacy of 400 mg Twice Daily Rifamycin SV MMX® Added to Standard Oral Rehydration Therapy (ORT) Versus Placebo Plus ORT, in the Treatment of Traveler's Diarrhea in Children Age 12 to 17 Years

Conditions
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Traveler's Diarrhea

Intervention / Treatment
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* Drug: Rifamycin SV MMX
* Drug: Placebo to Rifamycin SV-MMX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute bacterial diarrhea defined as at least 3 unformed stools within the 24 hours preceding randomization, with a duration of illness ≤72 h. The bacterial origin of diarrhea will be confirmed a posteriori by stool microbiology sampling at the time of screening. Presence of one or more signs or symptoms of enteric infection have to be present, including nausea, vomiting, abdominal cramps or pain, tenesmus, urgency History of recent travel from an industrialized country to a developing region with a known high incidence of travelers' diarrhea Male or female 12-17 years of age, providing an unformed pre-treatment stool Females of child-bearing potential must use an acceptable contraceptive method throughout the study treatment period The parent or legally acceptable representative guardian must provide informed consent for the subject. The Subject must also provide written informed assent by the parent or legal guardian at the time of assent/consent signing. Exclusion Criteria: Fever (>100.4ºF or 38ºC), or presence of signs and symptoms of systemic infection Females pregnant or breast feeding or not using adequate birth control Known or suspected infection with non-bacterial pathogen Symptoms of acute diarrhea of >72 hours duration Presence of grossly bloody stool Moderate to severe dehydration History of inflammatory bowel disease (IBD) Abdominal ileus Severe dehydration Greater than two doses of an antidiarrheal medication within 24 hours before randomization, or any symptomatic therapy within 2 hours before enrolment Receiving antimicrobial drug with expected activity against enteric bacterial pathogens within the week prior to enrolment Hypersensitivity to rifamycin-related antibiotics or to any excipient included in the study medications Subjects unable/unwilling to comply with study protocol Participation in a clinical trial within the last 30 days

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rifamycin SV MMX plus ORT<br>Each tablet contains 200mg Rifamycin SV MMX for oral administration | Drug: Rifamycin SV MMX<br>* 200 mg Rifamycin SV-MMX® (CB-01-11)<br>* Other names: Rifamycin;|
| Placebo Comparator: Placebo tablets plus ORT<br>Placebo tablets identical to Rifamycin tablets with respect to size, taste and appearance. | Drug: Placebo to Rifamycin SV-MMX<br>* Placebo to Rifamycin SV-MMX® Placebo tablets correspond to active tablets with respect to size, taste, and appearance.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure | Passage of two or fewer soft stools and no watery stools, no fever (> 100.4 ºF or 38 ºC), and no signs or symptoms of enteric infection (other than mild excess gas/flatulence) during a 24-hour interval in the 120-hour data collection period after the first dose of study drug or Passage of no stools or only formed stools and no fever during a 48-hour interval in the 120-hour data collection period after the first dose of study drug, with or without other signs or symptoms of enteric infection. | 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Last Unformed Stool (TLUS) | defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared. Subjects who meet the criteria for clinical cure immediately after the start of the study and prior to passing any unformed stools are defined as having a TLUS of 0 hours. Subject who terminated the study early due treatment failure will have a censored TLUS set to 120 hours. | 120 hours | 
| Microbiological Cure | the proportion of subjects with an identified pathogen at baseline with microbiological eradication in the post-treatment stool sample. | 120 hours | 
| Treatment Failure | Defined as either of the following: Worsening diarrhea and/or signs or symptoms of enteric infection or failure to improve 24 hours or more after the first dose of study drug that results in administration of rescue therapy and/or Not achieving Clinical Cure in the 120-hr data collection period after the first dose of study drug or use of antimicrobial prohibited concomitant medication. | 120 hours | 
| Improvement | Defined as ≥ 50% reduction in the number of unformed stools passing during a 24 h period, in comparison with the number of stools passed during the 24 h immediately before enrolment in the study. | 24 hours |