One Year Study of Rifaximin Delayed Release (DR) in Crohn's Disease

A Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Multiregional, One Year Study to Assess the Efficacy and Safety of Twice Daily Oral Rifaximin Delayed Release Tablets for Induction of Clinical Remission With Endoscopic Response at 16 Weeks Followed by Clinical and Endoscopic Remission at 52 Weeks in Subjects With Active Moderate Crohn's Disease

The primary objective is to determine the efficacy of rifaximin DR also referred to as Extended Intestinal Release (EIR) tablets vs. placebo for the induction of clinical remission and endoscopic response following 16 weeks of treatment in participants presenting with active moderate Crohn's disease. A key secondary objective is to evaluate clinical and endoscopic remission following an additional 36 weeks of treatment.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Rifaximin EIR; Drug: Placebo

Detailed Description

RECD3126 is a double-blind, placebo-controlled, parallel-group, multicenter, multiregional, 52-week study to assess the efficacy and safety of rifaximin DR tablets for the induction of clinical remission and endoscopic response at 16 weeks followed by clinical and endoscopic remission after 52 weeks of continuous therapy in participants with active moderate Crohn's disease.

Participants will be randomized in a 1:1 allocation to rifaximin or placebo at the beginning of the treatment period and will maintain treatment assignment throughout the duration of the study. Ileocolonoscopy will be performed on all participants at baseline, between Weeks 16 and 17 (end of the Induction Phase), and following completion of the 36-week Long Term Treatment Phase (Week 52).

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
  • Arizona
    • Tucson, Arizona, United States, 85712
    • Tucson, Arizona, United States, 85741
    • Tucson, Arizona, United States, 85710
  • Arkansas
    • Sherwood, Arkansas, United States, 72120
  • California
    • Garden Grove, California, United States, 92845
    • La Jolla, California, United States, 92037
    • La Mirada, California, United States, 90638
    • Laguna Hills, California, United States, 92653
    • Los Angeles, California, United States, 90045
    • Northridge, California, United States, 91324
    • Oceanside, California, United States, 92056
    • San Diego, California, United States, 92103
  • Colorado
    • Littleton, Colorado, United States, 80120
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • Boca Raton, Florida, United States, 33428
    • Clearwater, Florida, United States, 33756
    • Coral Gables, Florida, United States, 33173
    • Hollywood, Florida, United States, 33021
    • Inverness, Florida, United States, 34452
    • Lauderdale Lakes, Florida, United States, 33319
    • Maitland, Florida, United States, 32751
    • Miami, Florida, United States, 33173
    • Miami, Florida, United States, 33136
    • Miami, Florida, United States, 33144
    • Miami Springs, Florida, United States, 33166
    • Orange Park, Florida, United States, 32073
    • Orlando, Florida, United States, 32803
    • Palm Harbor, Florida, United States, 33781
    • Port Orange, Florida, United States, 32127
    • Tampa, Florida, United States, 33603
  • Georgia
    • Athens, Georgia, United States, 30606
    • Atlanta, Georgia, United States, 30322
    • Atlanta, Georgia, United States, 30338
    • Macon, Georgia, United States, 31201
  • Illinois
    • Chicago, Illinois, United States, 60624
    • Evanston, Illinois, United States, 60201
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
  • Louisiana
    • Shreveport, Louisiana, United States, 71102
    • West Monroe, Louisiana, United States, 71291
  • Maryland
    • Hagerstown, Maryland, United States, 21742
    • Hollywood, Maryland, United States, 20636
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
  • Michigan
    • Caro, Michigan, United States, 48723
    • Stevensville, Michigan, United States, 49127
    • Wyoming, Michigan, United States, 49519
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
  • Mississippi
    • Ocean Springs, Mississippi, United States, 39564
    • Tupelo, Mississippi, United States, 60624
  • Missouri
    • Bridgeton, Missouri, United States, 63044
    • Creve Coeur, Missouri, United States, 63141
  • New Jersey
    • Vineland, New Jersey, United States, 08360
    • Voorhees, New Jersey, United States, 08043
  • New York
    • New York, New York, United States, 10016
    • New York, New York, United States, 10032
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
    • Kinston, North Carolina, United States, 28501
  • Ohio
    • Beavercreek, Ohio, United States, 45440
    • Cincinnati, Ohio, United States, 45219
    • Columbus, Ohio, United States, 43210
    • Kettering, Ohio, United States, 45429
    • Lima, Ohio, United States, 45806
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
  • Oregon
    • Portland, Oregon, United States, 97210
  • South Carolina
    • Columbia, South Carolina, United States, 29203
    • Fort Mill, South Carolina, United States, 29707
  • Texas
    • Dallas, Texas, United States, 75231
    • Houston, Texas, United States, 77036
    • Houston, Texas, United States, 77099
    • Humble, Texas, United States, 77338
    • San Antonio, Texas, United States, 78229
    • Tyler, Texas, United States, 75701
  • Utah
    • Ogden, Utah, United States, 84405
    • West Jordan, Utah, United States, 84088
    • West Valley City, Utah, United States, 84120
  • Virginia
    • Chesapeake, Virginia, United States, 23320
  • Washington
    • Richland, Washington, United States, 99352

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Major Inclusion Criteria:

• Moderate, non-fistulizing Crohn's disease in the ileum and/or colon prior to randomization; and a SES-CD score of ≥7 (confirmed by centralized endoscopy reading).
• During the screening period, the participant will need to have certain average daily scores for abdominal pain and average number of liquid/very soft stools.

Major Exclusion Criteria:

• Pregnant or lactating females. Females of childbearing (reproductive) potential must have a negative serum pregnancy test at screening and agree to use a highly effective method(s) of contraception throughout their participation in the study. Diagnosis of ulcerative or indeterminate colitis.
• Diagnosis of Celiac Disease.
• Bowel surgery within 12 weeks prior to screening and/or has surgery planned or deemed likely for Crohn's disease during the study period.
• Presence of an ileostomy or colostomy.
• Known fixed symptomatic stenosis/stricture of the small or large bowel.
• Had more than one segmental colonic resection.
• Had more than 3 small bowel resections or symptoms associated with short bowel syndrome.
• Current evidence of peritonitis.
• History or evidence of colonic mucosal dysplasia.
• History or evidence of adenomatous colonic polyps that have not been removed.
• Unwilling to be tapered off corticosteroids by Week 8 or the participant is known by the Investigator to be steroid-dependent.
• Has used a biologic within 12 weeks of randomization.
• Used cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or similar drugs within 8 weeks prior to randomization.
• Had rectal administration of 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/foams/ suppositories within 2 weeks prior to screening visit.

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
Experimental: Rifaximin EIR 800 mg; Participants will receive rifaximin EIR 400 milligrams (mg) tablets orally twice daily for 52 weeks.	Drug: Rifaximin EIR; Rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.
Placebo Comparator: Placebo; Participants will receive placebo matching to rifaximin EIR tablets orally twice daily for 52 weeks.	Drug: Placebo; Placebo matching to rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 16	Clinical symptom remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 16 visit being less than or equal to (≤) 10 (from CDAI Item 1). CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 16
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at Week 16	Clinical Symptom Remission defined by (2) an abdominal pain (graded from 0 [less severe]-3 [more severe]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 16 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 16
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 16	Clinical Symptom Remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 16 visit being ≤ 10 (from CDAI Item 1); and (2) an abdominal pain (graded from 0 [less severe]-3 [more severe]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 16 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 16
Number of Participants With Endoscopic Response Between Week 16 and 17	Endoscopic response defined as a ≥ 3-point decrease in the SES-CD from baseline to the SES-CD score obtained between Week 16 and Week 17. SES-CD scores were calculated from centrally-read digital video of ileocolonoscopies performed at baseline and between Week 16 and Week 17. SES-CD is a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.	Baseline, Week 16 to 17
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 52	Clinical symptom remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 52 visit being ≤ 10 (from CDAI Item 1). CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 52
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at Week 52	Clinical Symptom Remission defined by (2) an abdominal pain (graded from 0 [less severe]-3 [more severe]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 52 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 52
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 52	Clinical Symptom Remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 52 visit being ≤ 10 (from CDAI Item 1); and (2) an abdominal pain (graded from 0 [less severe]-3 [more severe]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 52 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 52
Number of Participants With Endoscopic Response at Week 52	Endoscopic response defined as a ≥ 3-point decrease in the SES-CD from baseline to the SES-CD score obtained at Week 52. SES-CD is a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Clinical Remission (Defined as CDAI Score of <150) at Week 16	Clinical remission was defined as a CDAI score of less than 150 points at Week 16. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	Week 16
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) Over Time	Clinical Symptom Remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to each clinical visit being ≤ 10 (from CDAI Item 1); and (2) an abdominal pain (graded from 0 [less severe]-3 [more severe]) rating of ≤ 1 (from CDAI Item 2) on each day for the last 7 days prior to each clinic visit in ≥ 80% of the study visits during the 52-week treatment period, including Week 52. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.	From Baseline to Week 52
Number of Participants With SES-CD Score of 0 at Week 52	SES-CD is a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.	Week 52

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Collaborators: Salix Pharmaceuticals, Inc. a division of Bausch Health US, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2014
• Primary Completion (Actual): October 6, 2017
• Study Completion (Actual): October 6, 2017

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 12, 2014
• First Posted (Estimate): September 15, 2014

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease; Crohn's Disease; Rifaximin; Clinical remission with endoscopic response
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: RECD3126