Study to Evaluate Safety and Efficacy of Rifamycin SV MMX in Treating Traveler's Diarrhea in Children Age 12 to 17 Years
Primary Purpose
Traveler's Diarrhea
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Rifamycin SV MMX
Placebo to Rifamycin SV-MMX
Sponsored by
About this trial
This is an interventional treatment trial for Traveler's Diarrhea
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rifamycin SV MMX plus ORT
Placebo tablets plus ORT
Arm Description
Each tablet contains 200mg Rifamycin SV MMX for oral administration
Placebo tablets identical to Rifamycin tablets with respect to size, taste and appearance.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Microbiological Cure
the proportion of subjects with an identified pathogen at baseline with microbiological eradication in the post-treatment stool sample.
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.
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.
Full Information
NCT ID
NCT04027894
First Posted
July 12, 2019
Last Updated
January 26, 2023
Sponsor
RedHill Biopharma Limited
1. Study Identification
Unique Protocol Identification Number
NCT04027894
Brief Title
Study to Evaluate Safety and Efficacy of Rifamycin SV MMX in Treating Traveler's Diarrhea in Children Age 12 to 17 Years
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2024 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RedHill Biopharma Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traveler's Diarrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
142 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rifamycin SV MMX plus ORT
Arm Type
Experimental
Arm Description
Each tablet contains 200mg Rifamycin SV MMX for oral administration
Arm Title
Placebo tablets plus ORT
Arm Type
Placebo Comparator
Arm Description
Placebo tablets identical to Rifamycin tablets with respect to size, taste and appearance.
Intervention Type
Drug
Intervention Name(s)
Rifamycin SV MMX
Other Intervention Name(s)
Rifamycin
Intervention Description
200 mg Rifamycin SV-MMX® (CB-01-11)
Intervention Type
Drug
Intervention Name(s)
Placebo to Rifamycin SV-MMX
Other Intervention Name(s)
Placebo
Intervention Description
Placebo to Rifamycin SV-MMX® Placebo tablets correspond to active tablets with respect to size, taste, and appearance.
Primary Outcome Measure Information:
Title
Clinical Cure
Description
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.
Time Frame
120 hours
Secondary Outcome Measure Information:
Title
Time to Last Unformed Stool (TLUS)
Description
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.
Time Frame
120 hours
Title
Microbiological Cure
Description
the proportion of subjects with an identified pathogen at baseline with microbiological eradication in the post-treatment stool sample.
Time Frame
120 hours
Title
Treatment Failure
Description
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.
Time Frame
120 hours
Title
Improvement
Description
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.
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilead Raday, M.Sc.
Phone
+972-3-6398893
Email
gilead@redhillbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
June Almenoff, MD, PhD
Organizational Affiliation
RedHill Biopharma, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate Safety and Efficacy of Rifamycin SV MMX in Treating Traveler's Diarrhea in Children Age 12 to 17 Years
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