Study to Evaluate Safety and Efficacy of Rifamycin SV Multi-Matrix System (MMX) for the Treatment of Traveler's Diarrhea (TD)

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Rifamycin SV MMX for the Treatment of Traveler's Diarrhea

The purpose of this study is to determine whether Rifamycin SV MMX is a safe and effective treatment for Traveler's Diarrhea.

Study Overview

• Status: Completed
• Conditions: Traveler's Diarrhea
• Intervention / Treatment: Drug: Placebo; Drug: Rifamycin SV MMX

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• Guatemala
  • Antigua, Guatemala, 03001
    • Santarus Investigational Site 03
  • Antigua, Guatemala
    • Santarus Investigational Site 14
  • Quetzaltenango, Guatemala, 09001
    • Santarus Investigational Site 04
• Mexico
  • Cabo San Lucas, Mexico, 23440
    • Santarus Investigational Site 12
  • Cancun, Mexico, 77500
    • Santarus Investigational Site 10
  • Oaxaca, Mexico, 6800
    • Santarus Investigational Site 07
  • Puebla, Mexico, 72197
    • Santarus Investigational Site 08
  • Puerto Escondido, Mexico, 71980
    • Santarus Investigational Site 09
  • Puerto Vallarta, Mexico, 48330
    • Santarus Investigational Site 11
  • Tulum, Mexico, 77760
    • Santarus Investigational Site 13
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 42670
      • Santarus Investigational Site 05
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62240
      • Santarus Investigational Site 06

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (two matching tablets) orally twice daily for 3 days (72 hours)	Drug: Placebo; Placebo (two matching tablets) orally twice daily for 3 days (72 hours).
Experimental: Rifamycin SV MMX; Rifamycin SV MMX® 400 mg (two 200 mg tablets) orally twice daily for 3 days (72 hours).	Drug: Rifamycin SV MMX; Rifamycin SV MMX® 400 mg (two 200 mg tablets) orally twice daily for 3 days (72 hours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Last Unformed Stool (TLUS)	The primary endpoint is TLUS defined as the interval in hours between the first dose of study drug and the last unformed stool passed just before the start of Clinical Cure. An unformed stool is defined as either a soft or watery stool. TLUS will be calculated for each patient in the following manner: Step 1: Identify when the patient achieves Clinical Cure. Step 2: Moving backwards from this time, identify the time of the last unformed stool. Step 3: The TLUS equals the time from the first dose of study drug to the time of the last unformed stool identified in Step 2.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure	Clinical Cure is defined as either of the following: Passage of two or fewer soft stools and no watery stools, no fever (>100.4 ºF or 38 ºC), and no signs or symptoms of enteric infection (other than mild excess gas/flatulence) during a 24 hour interval in the 120-hr data collection period after the first dose of study drug; Passage of no stools or only formed stools and no fever during a 48-hour interval in the 120-hr data collection period after the first dose of study drug, with or without other signs or symptoms of enteric infection	24 hours

Collaborators and Investigators

• Sponsor: Cosmo Technologies Ltd
• Collaborators: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Herbert DuPont, MD, Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: May 27, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 11, 2010

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: diarrhea; traveler's; Rifamycin SV MMX; Rifamycin; MMX; Traveler's Diarrhea
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Diarrhea; Dysentery; Anti-Infective Agents; Antirheumatic Agents; Anti-Bacterial Agents; Rifamycins; Rifamycin SV
• Other Study ID Numbers: C2009-0201