A Randomized, Open-Label Study to Assess Pharmacokinetics of Xifaxan® 200 mg in Pediatric Subjects 6 to 11 Years of Age With Acute Diarrhea of Suspected Bacterial Etiology, and the Safety and Efficacy of Xifaxan® 200 mg Plus Oral Rehydration Therapy (ORT) Compared to ORT Alone
Overview
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Bausch Health Americas, Inc.
- Enrollment
- 54
- Locations
- 5
- Primary Endpoint
- Peak Plasma Concentration (Cmax) of Rifaximin
Overview
Brief Summary
The goal of this clinical trial is to learn how rifaximin 200 mg is processed in the body (pharmacokinetics) in children 6 to 11 years old with acute diarrhea that may be caused by bacteria. It will also learn about the safety and effectiveness of rifaximin when given with oral rehydration therapy (ORT) compared with ORT alone. The main questions it aims to answer are:
How does rifaximin 200 mg move through and leave the body in children with acute diarrhea?
Is rifaximin safe for children in this age group?
Does rifaximin plus ORT help resolve diarrhea faster than ORT alone?
Researchers will compare rifaximin plus ORT to ORT alone to see if adding rifaximin improves outcomes.
Participants will:
Take one rifaximin 200 mg tablet + ORT three times a day for 3 days or receive ORT alone
Receive oral rehydration therapy according to the investigator's standard of care
Attend up to 4 clinic visits over 5 days and receive 4 follow-up phone calls
Provide blood samples on Day 1 and Day 3 for pharmacokinetic testing (rifaximin group only)
Provide stool samples to identify bacterial pathogens
Keep a diary of stool frequency and consistency to help determine when diarrhea resolves
Be monitored for side effects, vital signs, and laboratory changes
Detailed Description
This study is a randomized, open-label clinical trial designed to evaluate the pharmacokinetics, safety, and efficacy of rifaximin 200 mg in pediatric participants aged 6 to 11 years with acute diarrhea of suspected bacterial etiology. Acute diarrhea may be caused by bacterial infections such as E. coli, Shigella, Salmonella, or Campylobacter.
Participants are randomly assigned to receive either rifaximin 200 mg plus oral rehydration therapy (ORT) or ORT alone. Participants in the rifaximin group take one tablet three times a day for 3 days, in addition to ORT according to the investigator's standard of care. Participants in the ORT-alone group receive ORT only.
The primary objective is to assess how rifaximin is absorbed, distributed, and eliminated in children (pharmacokinetics). Secondary objectives include evaluating the safety and tolerability of rifaximin and assessing whether rifaximin plus ORT helps resolve diarrhea faster than ORT alone.
Safety assessments include monitoring adverse events, vital signs, and laboratory tests (hematology, chemistry, and urinalysis). Participants or their caregivers keep a daily diary to record stool frequency and consistency, time to last unformed stool, and any related symptoms such as abdominal cramps, nausea, vomiting, or flatulence. Stool samples are collected to identify the bacterial pathogen(s) causing diarrhea.
Pharmacokinetic assessments are conducted in participants receiving rifaximin plus ORT, with blood samples collected on Day 1 and Day 3: pre-dose, 1 hour post-dose, and 8 hours post-dose. Plasma samples are analyzed for rifaximin and 25-desacetyl rifaximin to determine pharmacokinetic parameters, including maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve (AUC).
Participants attend up to four clinic visits over the 5-day study period and receive follow-up phone calls on Days 6, 7, 8, and 30 to monitor safety and collect diary information. Compliance with study drug and ORT administration is assessed throughout the study.
This study is designed to provide information on rifaximin pharmacokinetics, its safety in children, and the potential benefit of rifaximin plus ORT in resolving acute diarrhea of suspected bacterial origin.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 6 Years to 12 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Consent and assent are appropriately obtained prior to any study related activities, including discontinuation of any prohibited medications (subjects must sign an assent for the study and a parent or a legal guardian must sign the informed consent).
- •Subject is between 6 to 11 (and 11 months) years of age, inclusive, and weighs at least 15 kg (33 lbs) at Screening.
- •Females of childbearing (reproductive) potential must have a negative urine and serum pregnancy test at Screening and agree to use a highly effective method of contraception throughout their participation in the study. Acceptable methods of contraception are those alone or in combination, that result in a low failure rate (ie, less than 1% per year) when used consistently and correctly and include hormonal methods (oral, injected or implanted), intrauterine device or intrauterine system or double barrier methods (simultaneous use of a physical barrier method by the subject and male partner, including a male condom and an occlusive cap \[diaphragm or cervical/vault cap\] with spermicidal). Abstinence or partner(s) with a vasectomy may be considered an acceptable method of contraception at the discretion of the Investigator.
- •NOTE: Female subjects are considered of child-bearing potential if they are (a) physiologically capable of becoming pregnant, defined as a female who has experienced menarche and (b) they will be, or could possibly be, engaging in sexual activity during the course of the study.
- •Subject has diarrhea of suspected bacterial etiology defined by:
- •At least 3 unformed stools in the last 24 hours prior to Screening.
- •A fever ≥ 100.4°F (38°C) and ≤ 102.2°F (39°C) or has had a fever of ≥ 100.4°F (38°C) and ≤ 102.2°F (39°C) at any time since the development of abdominal pain or diarrhea.
- •Illness for less than 96 hours at Screening.
- •Parent or legal guardian and subject, when applicable based on aged, are capable of understanding the requirements of the study and willing to comply with all study procedures and visits.
Exclusion Criteria
- •Subject has a history of chronic diarrhea.
- •Subject is unable to eat or drink.
- •Subject has at least one of the following signs or symptoms:
- •Presence of fever \>39°C (\>102.2°F).
- •Presence of frank blood in stool.
- •Subject has taken \>2 doses of anti-diarrheal therapies in the 24 hours prior to randomization.
- •Subject has taken any oral antimicrobial drug within 14 days of randomization.
- •Subject has an unstable medical condition, in the opinion of the Investigator, (including, but not limited to, evidence of severe dehydration noted by tachycardia, abnormal blood pressure, or decreased skin turgor) at the Screening visit.
- •Subject has known, clinically significant hepatic disease manifested by twice the age and sex-adjusted upper limit of normal (2 × ULN) for any of the following liver function tests: alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, or total bilirubin (except in isolated elevation of unconjugated bilirubin).
- •Subject has known, clinically significant renal disease (eg, 1.5 × ULN of serum creatinine or 2 × ULN of blood urea nitrogen levels).
Arms & Interventions
Rifaximin 200 mg + ORT
rifaximin 200 mg tablets orally three times daily for 3 days plus oral rehydration therapy (ORT) administered per investigator standard of care
Intervention: Rifaximin 200 mg Tablet (Drug)
Rifaximin 200 mg + ORT
rifaximin 200 mg tablets orally three times daily for 3 days plus oral rehydration therapy (ORT) administered per investigator standard of care
Intervention: Oral Rehydration Therapy (ORT) (Other)
ORT Alone
ORT administered per investigator standard of care without rifaximin.
Intervention: Oral Rehydration Therapy (ORT) (Other)
Outcomes
Primary Outcomes
Peak Plasma Concentration (Cmax) of Rifaximin
Time Frame: Days 1 and 3
Cmax levels following rifaximin 200 mg + ORT
Time to Maximum Plasma Concentration (Tmax) of Rifaximin
Time Frame: Days 1 and 3
Tmax for rifaximin following rifaximin 200 mg + ORT
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-τ) for Rifaximin
Time Frame: Days 1 and 3
Area under the concentration-time curve over the dosing interval
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) for Rifaximin
Time Frame: Days 1 and 3
Area under the concentration-time curve to last measurable concentration
Proportion of participants with Clinical Cure
Time Frame: Up to Day 5 (End of Treatment)
Proportion of participants achieving clinical cure, defined as either: 1. No unformed stools within a 48-hour period with no fever (with or without other clinical symptoms such as abdominal cramps or pain, excess gas/flatulence, nausea, vomiting, urgency, tenesmus); or 2. No watery stools and no more than two soft stools within a 24-hour period with no fever and no other clinical symptoms except for mild excess gas/flatulence.
Secondary Outcomes
- Incidence of Treatment-Emergent Adverse Events (AEs)(Day 1-30)
- Time to Last Unformed Stool (TLUS)(Up to Day 5 (End of Treatment))
- Change From Baseline in Clinical Laboratory Parameters(Day 1-30)
- Change From Baseline in Vital Signs(Day 1-30)