Trial Evaluating Chemoprophylaxis Against Travelers' Diarrhea - Prevent TD

The primary efficacy outcome will be assessed by review of the symptom memory aid (TravMil
diary). Subjects will follow a symptom memory aid from the onset of a disease episode and
record relevant symptomatology (date/time and number of diarrheal episodes, associated
symptoms such as fever, vomiting, nausea, bloody stools and cramps, severity of symptoms,
functional activity). Use of antibiotics and/or Imodium (loperamide) for each episode will
also be recorded). An additional memory aid to capture occurrence of solicited adverse
events, use of new prescription medications, as well as adherence to study medication regimen
will be utilized by subjects during deployment and returned (or re-created with study
personnel if lost or incomplete) at follow-up Memory aid data will be actively sought from
all subjects via required in-person follow-up.

Secondary efficacy outcomes will also largely be derived from the self-report of subjects via
use of the memory aid data. Secondary safety evaluation will be performed at the end of study
visit based on history obtained from the subject regarding medical treatment requiring events
while deployed.

Individuals will be enrolled prior to travel/deployment. At the time of enrollment they will
undergo eligibility criteria review, informed consent process, baseline assessment
(demographics, medical history, others), sample collection (blood and stool), and blinded
randomization into a study arm.

Episodes of diarrhea are expected to occur while on study drug. Subjects will be instructed
and expected to seek care for these episodes from medical assets available to them at COD.

Subjects will be instructed to discontinue study drug if they develop diarrhea and are given
antibiotic therapy. It is not expected that study drug will impact the choice or
effectiveness of antibiotics used to treat travelers' diarrhea. Some subjects will be
eligible to restart (only once restart) study drug once they are cured of a travelers'
diarrhea episode. See US and UK addenda for details.

The end of prophylaxis is defined as the +/- 96hr period from cessation of prophylaxis due to
(A) the subject completing maximal period of prophylaxis but remains deployed, or (B) being
re-deployed and returns to mainland/COO. During this end of prophylaxis period, subjects may
be seen by study personnel and perform an end of prophylaxis visit.

The post-deployment period is defined as the return to COO through 8 weeks from return. A
post-deployment visit, in the COO will be planned for all subjects enrolled in the study and
will occur as soon as it can be scheduled.

All subjects will be asked to complete a baseline questionnaire on day of enrollment and
complete web-based surveys during the follow-up period. Subjects will be emailed the survey
link at 3 and 6 months post-return to COO. The survey will assess for several types of
functional bowel disorders and symptoms of ReA using standardized questions and definitions
and questions and will use disease activity scales to assess impact on daily life.

A sample of blood will be collected up to 2 times as part of participation in this study. The
samples will be collected, processed and stored until transported at a later date to central
lab for testing of acute and convalescent titers directed against bacterial and viral
enteropathogens. Samples will also be used for biomarker evaluation and support of
exploratory objectives.

Stool samples will be used for exploratory microbiological analyses to assess etiology of
diarrhea by pathogen, antibiotic susceptibility of enteropathogens, and evaluation of impact
of rifaximin on the microbiome. Serum will be utilized to attempt to determine seroconversion
status for pathogens not identified during stool analysis.

Inclusion Criteria:

1. An Institutional Review Board (IRB) / Ethics Committee (EC)-approved informed consent
form is signed and dated.

2. Subject is at least 18 years of age

3. Subject's duration of prophylaxis will be least 2 weeks.

4. Subject is capable of and willing to comply with all study procedures and available
for the end of study visits and sample collection at COO (within 6 months from start
of prophylaxis).

5. Women: Non-nursing and negative urine/serum pregnancy test with understanding (through
informed consent process) to avoid pregnancy while on study drug. Sole reliance on
oral contraceptives (OCPs) for birth control will not be recommended (see section
6.3.2.1.) Should an individual have a documented surgical sterilization in her medical
record, a pregnancy test will not be required. If a volunteer becomes pregnant during
the study, the principal investigator will notify the study research monitor and the
IRBs. The pregnancy outcome will be followed per IRB and other regulatory requirements
for US and UK personnel.

6. (For US Personnel Only). Have consented to participate in TravMil protocol.

Exclusion Criteria:

1. Subject received any systemic or gastrointestinal antibiotic in the 7 days prior to
enrollment (except anti-malarial prophylaxis agents).

2. Subject has hypersensitivity or allergy to rifaximin or rifampicin.

3. Subject has acute diarrhea within 7 days prior to enrollment

4. Subject has a concomitant disease or condition that could interfere with, or for which
treatment could interfere with, the conduct of the study, or could in the opinion of
the investigator increase the risk of AEs during the subject's participation in the
study

5. Subject is currently taking or plans to take during deployment at least one of the
following medications: theophylline or warfarin (Coumadin).