Study to Evaluate Safety and Efficacy of Rifamycin SV Multi-Matrix System (MMX) for the Treatment of Traveler's Diarrhea (TD)
Study to Evaluate Safety and Efficacy of Rifamycin SV Multi-Matrix System (MMX) for the Treatment of Traveler's Diarrhea (TD)
The purpose of this study is to determine whether Rifamycin SV MMX is a safe and effective
 treatment for Traveler's Diarrhea.
This is a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study
 conducted in patients traveling to developing regions with a known high incidence of TD.
 Eligibility will be based on a symptom complex that is highly indicative of enteric acute
 bacterial infection without indication of systemic infection.

 Approximately 262 patients will be enrolled in the study and randomized at a 3:1 ratio to
 receive Rifamycin SV MMX® 400 mg or placebo orally twice daily for 3 days (72 hours).
 Treatment will be initiated on the day of Screening (Visit 1, Day 1), within 72 hours of
 onset of diarrhea. Daily doses of study drug will be taken at breakfast time and dinner time
 with a glass of liquid.

 Safety and efficacy will be assessed.

 Blood samples for routine safety tests (chemistry and hematology) will be collected at Visit
 1 and at Visit 3 and sent to a local laboratory for analysis and reporting to the
 Investigator for safety monitoring. Urine samples for routine urinalysis (dipstick only) will
 be collected at Visits 1 and 3, and the results will be used by the Investigator for safety
 monitoring.

 If a patient's diarrhea and/or signs or symptoms of enteric infection worsen in a 24 hour
 interval of time during the treatment period or if the enteric illness fails to improve after
 24 hours or more of therapy, the patient may receive Rescue Therapy. Rescue Therapy will be
 prescribed by the Investigator using local standard empiric therapy and/or guided by pathogen
 identification.
Inclusion Criteria

 Patients were enrolled in the study only if they met all of the following criteria:

 1. Male and female patients 18 years of age or older

 2. Female and male patients of childbearing potential must have agreed to use an
 effective method of birth control (this method must have been approved by the
 investigator and may have included total abstinence from sexual intercourse) during
 the treatment and follow-up study periods; female patients of childbearing potential
 must have had a negative pregnancy test in the 72 hours before randomization; female
 patients who abstained totally from sexual intercourse were not required to take the
 pregnancy test

 3. Recent travel (i.e., must be within 30 days of randomization) from an industrialized
 country

 4. Experiencing signs or symptoms indicative of acute bacterial diarrhea (TD), defined as
 at least three unformed, watery or soft, stools within the 24 hours preceding
 randomization and the duration of illness 72 hours before randomization, and able to
 provide an unformed stool sample during Screening (the latter can be the third
 unformed stool passed by the patient within the 24 hours preceding randomization); the
 bacterial cause of diarrhea was confirmed by microbiology analysis of the stool sample

 5. Experiencing one or more signs or symptoms of enteric infection (moderate to severe
 gas/flatulence, nausea, vomiting, abdominal cramps or pain, rectal tenesmus, or
 defecation urgency)

 6. Capable of and willing to give informed consent

 Exclusion Criteria

 Patients were excluded from the study if they met any of the following criteria:

 1. Fever (> 100.4F or 38C) or presence of signs and symptoms of systemic infection Note:
 antipyretic medication should not have been administered in the 6 hours before this
 assessment

 2. Known or suspected infection with non-bacterial pathogen before randomization

 3. Presence of diarrhea for > 72 hours duration

 4. Presence of grossly bloody stool

 5. Presence of moderate to severe dehydration (i.e., presence of orthostatic hypotension
 and/or dehydration requiring treatment with intravenous fluids)

 6. History of ulcerative colitis, diarrhea-predominant irritable bowel syndrome, Crohn's
 disease, celiac sprue (gluten-enteropathy), chronic pancreatitis, malabsorption, or
 any other gastrointestinal disease associated with diarrhea. Note: lactose intolerance
 treated with lactase supplements or a lactose-free diet were not excluded if these
 regimens were maintained during the study.

 7. Receiving more than two doses of an antidiarrheal medication (e.g., antimotility,
 absorbent, adsorbent, antisecretory, or probiotics) within 24 hours before
 randomization

 8. Receiving one or more of the following antibiotics, which are active against gram
 negative bacteria TMP-SMX, fluorquinolone, azithromycin or rifaximin within 7 days
 before randomization

 9. Females pregnant or breast feeding or not using adequate birth control

 10. Known intolerance/hypersensitivity/resistance to rifamycin or rifamycin-related
 antibiotics or to any excipient included in the study medications

 11. Patients unable or unwilling to comply with study protocol (e.g., alcoholism, mental
 illness, travel schedule)

 12. Participation in a clinical study with another investigational drug in the 30 days
 prior to randomization or while participating in this study

 13. Previous participation in this study