Rifaximin plus oral rehydration for children 6–11 with acute diarrhea

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