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

Traveler's Diarrhea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01142089
• Other study ID #: C2009-0201
• Status: Completed
• Phase: Phase 3
• Start date: May 27, 2010
• Est. completion date: June 2012

Study information

• Verified date: April 2018
• Source: Cosmo Technologies Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 264
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diarrhea
• Dysentery
• Traveler's Diarrhea

Intervention

Drug:
• Placebo
Placebo (two matching tablets) orally twice daily for 3 days (72 hours).
• Rifamycin SV MMX
Rifamycin SV MMX® 400 mg (two 200 mg tablets) orally twice daily for 3 days (72 hours).

Locations

Country	Name	City	State
Guatemala	Santarus Investigational Site 03	Antigua
Guatemala	Santarus Investigational Site 14	Antigua
Guatemala	Santarus Investigational Site 04	Quetzaltenango
Mexico	Santarus Investigational Site 12	Cabo San Lucas
Mexico	Santarus Investigational Site 10	Cancun
Mexico	Santarus Investigational Site 06	Cuernavaca	Morelos
Mexico	Santarus Investigational Site 05	Guadalajara	Jalisco
Mexico	Santarus Investigational Site 07	Oaxaca
Mexico	Santarus Investigational Site 08	Puebla
Mexico	Santarus Investigational Site 09	Puerto Escondido
Mexico	Santarus Investigational Site 11	Puerto Vallarta
Mexico	Santarus Investigational Site 13	Tulum

Sponsors (2)

Lead Sponsor	Collaborator
Cosmo Technologies Ltd	Valeant Pharmaceuticals International, Inc.

Countries where clinical trial is conducted

Guatemala,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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