Acute Diarrhea, Bacterial Infection, Diarrhea, Gastroenteritis
Conditions
Keywords
pediatric, children, rifaximin, xifaxan, Oral Rehydration Therapy (ORT), acute diarrhea, bacterial diarrhea, gastroenteritis, open-label, randomized, ages 6-11, diarrhea
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 is a randomized, open-label study to assess the pharmacokinetics of Xifaxan® 200 mg in pediatric participants 6 to 11 years of age with acute diarrhea of suspected bacterial etiology, and safety and efficacy Xifaxan® 200 mg plus ORT compared to ORT alone. Participants will receive Xifaxan® 200mg (1 tablet) TID plus oral rehydration therapy (ORT) or ORT alone as per the Investigator's Standard of Care (SOC) for administering ORS for three days. Participants will complete 3 or 4 study visits during the study; Screening (Day -2 to Day 1), Day 1, Day 3 (End of Treatment), and Day 5 (Last Clinic Visit), and 2 safety follow-up phone calls; Once during Day 6 to 8, and on Day 30 (End of Study). Participants may complete both Screening and Day 1 on the same day. At the Screening visit, participants will provide a stool sample for PCR testing to identify the bacterial pathogen isolated. During the 5-day study period, the participant or their caregiver will complete a diary to record the dose, the time of dosing, time and consistency of stools, and incidence of symptoms as defined above. In addition, the participant or the caregiver will record any AEs in the eDiary from Day 4 to Day 30 with Day 1 to Day 3 assessed during study visits. Participants in the Xifaxan® 200 mg plus ORT arm will undergo two 6 to 8-hour pharmacokinetic sampling periods, the first following the first dose on Day 1 and the second following the first dose on Day 3. During these sampling periods, 3 blood samples (approximately 4 mL each) will be collected for analysis of rifaximin and 25- desacetyl rifaximin plasma concentrations at the following times: pre-dose, 1 hour (+/- 10 minutes) and no less than 6 but no more than 8 hours following the first dose of the day.
Interventions
DRUGRifaximin 200 mg Tablet
Participants receive rifaximin 200 mg tablets orally three times daily (TID) for 3 days in combination with oral rehydration therapy (ORT). Blood samples for pharmacokinetic analysis are collected on Day 1 and Day 3 at pre-dose, 1 hour post-dose, and 6 to 8 hours post-dose.
Participants receive oral rehydration solution according to the investigator's standard of care. This is administered either alone (for the ORT-alone arm) or in combination with rifaximin (for the rifaximin + ORT arm). Participants or caregivers complete a daily diary documenting stool frequency, stool consistency, and related symptoms.
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
4.1 Inclusion Criteria A participant will be eligible for inclusion in this study if all of the following criteria are met: 1. Parent/legally authorized representative and participant, as applicable, have provided written informed consent/assent, are able to understand, and agree to comply with, all study procedures and requirements. 2. Participant is between 6 to 11 years of age (inclusive) 3. Participant weighs at least 15 kg (33 lbs) at Screening 4. Participant is able to swallow pills 5. Participant has diarrhea of suspected bacterial etiology defined by: 1. At least 3 unformed stools in the last 24 hours prior to Screening 2. Illness for less than 96 hours at Screening 3. Clinical presentation consistent with acute infectious diarrhea of suspected bacterial etiology 6. The participant agrees to use a highly effective method of contraception (if applicable) and to have urine pregnancy tests. Applies to females of childbearing potential (defined as postmenarche). Participants must practice at least 1 of the following medically acceptable methods of birth control throughout the study: Applicable to: All Post-Menarche Female Particpants: * Highly effective hormonal contraception methods such as oral, implantable, injectable, vaginal ring, or transdermal contraception for a minimum of 1 full cycle (based on the participant's usual menstrual cycle period) before study drug administration. * Total abstinence from sexual intercourse since the last menses before screening and agrees to total abstinence from screening until at least 30 days after last study drug administration. * Intrauterine device. All Males Participants: * Condoms with spermicide. * Total abstinence from sexual intercourse from screening visit until at least 30 days after last study drug administration. 4.2
Exclusion criteria
A participant will not be eligible for inclusion in this study if any of the following criteria are met: 1. Participant has a history of chronic diarrhea (defined as loose or watery stools persisting for at last 4 consecutive weeks) within 12 months prior to onset of current acute illness. 2. Participant is unable to eat or drink. 3. Participant has clinical features suggestive of invasive or severe bacterial diarrhea requiring alternative therapy (e.g., frank blood in stool, mucoid diarrhea with systemic symptoms such as high fever, severe abdominal cramping or tenderness, or signs of sepsis). 4. Participant has taken \>2 doses of anti-diarrheal therapies in the 24 hours prior to randomization. 5. Participant has taken any oral antimicrobial drug within 14 days of randomization. 6. Participant has a clinically significant or 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. 7. Participant has a known hypersensitivity or allergy to Xifaxan®, rifampin, rifamycin-derived antibiotics, or any of the components of the rifaximin (Xifaxan®) formulations used in this study. 8. Participant is pregnant or lactating or plans to become pregnant during the study. 9. Participant has had a previous history of malignancy. 10. Participant has a history of tuberculosis infection and/or has received treatment for tuberculosis infection. 11. Participant has any concurrent illness, disability or circumstance that may affect the interpretation of clinical data, could cause noncompliance with treatment or visits or otherwise contraindicates participation in this study in the opinion of the Investigator. 12. Participant has had significant blood loss within the 30 days prior to the Screening visit which prevents the collection of the blood volume required for this study. 13. Participant has participated in an investigational drug or device study within the 30 days prior to randomization. 14. Participant is an immediate household family member of study site personnel directly involved in the conduct of this study. 15. Participant is taking a medication that is prohibited per Section 4.5 (Prohibited Therapy). The following therapies are prohibited from Screening through Day 5: * Anti-diarrheal medications, including: * Anti-motility agents (eg, loperamide, diphenoxylate, codeine, and paregoric). * Absorbent agents (eg, cholestryramine). * Anti-secretory agents (eg, bismuth subsalicylate, octreotide, and vapreotide). * Probiotics * Any antimicrobial agents with an expected activity against enteric bacterial pathogens * A P-glycoprotein (P-gp) inhibitor * Warfarin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of Rifaximin | Days 1 and 3 | Cmax levels following rifaximin 200 mg + ORT |
| Time to Maximum Plasma Concentration (Tmax) of Rifaximin | Days 1 and 3 | Tmax for rifaximin following rifaximin 200 mg + ORT |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) for Rifaximin | Days 1 and 3 | Area under the concentration-time curve to last measurable concentration |
| Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-τ) for Rifaximin | Days 1 and 3 | Area under the concentration-time curve over the dosing interval |
| Proportion of participants with Clinical Cure | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Last Unformed Stool (TLUS) | Up to Day 5 (End of Treatment) | Time in hours from the first dose of study treatment to the last unformed stool, after which clinical cure is declared, based on subject/caregiver diary entries. |
| Incidence of Treatment-Emergent Adverse Events (AEs) | Day 1-30 | Number and percentage of participants with AEs and SAEs |
| Change From Baseline in Clinical Laboratory Parameters | Day 1-30 | Changes in hematology, chemistry, and urinalysis values |
| Change From Baseline in Vital Signs | Day 1-30 | Change in temperature, blood pressure, and pulse |
Countries
United States
Contacts
CONTACTAngela Moore
CONTACTMaryanne Santilli
Outcome results
None listed