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

NCT02240121 | Terminated Phase 3 Results

• 1 other identifier: RECD3125
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 72

Brief Summary

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.

Conditions

Crohn's Disease

Keywords

Crohn's Disease; Rifaximin; Clinical remission with endoscopic response; Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (8)

• 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 ≤ 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 Outcomes (3)

• Number of Participants Who Achieved Clinical Remission (Defined as CDAI Score of <150) at Week 16

  Week 16

• Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) Over Time

  From Baseline to Week 52

• Number of Participants With SES-CD Score of 0 at Week 52

  Week 52

Study Arms (2)

Rifaximin EIR 800 mg

EXPERIMENTAL

Participants will receive rifaximin EIR 400 milligrams (mg) tablets orally twice daily for 52 weeks.

Drug: Rifaximin EIR

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to rifaximin EIR tablets orally twice daily for 52 weeks.

Drug: Placebo

Interventions

Rifaximin EIR DRUG

Rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.

Rifaximin EIR 800 mg

Placebo DRUG

Placebo matching to rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bausch Health Americas, Inc.: lead
• Salix Pharmaceuticals, Inc. a division of Bausch Health US, LLC: collaborator

Study Sites (72)

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Scottsdale, Arizona, 85260, United States

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Tucson, Arizona, 85712, United States

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Tucson, Arizona, 85724, United States

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Little Rock, Arkansas, 72205, United States

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Little Rock, Arkansas, 72211, United States

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North Little Rock, Arkansas, 72117, United States

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Bakersfield, California, 93301, United States

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Los Angeles, California, 90067, United States

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Mission Hills, California, 91345, United States

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Orange, California, 92868, United States

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San Carlos, California, 94070, United States

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Torrance, California, 90503, United States

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Denver, Colorado, 80045, United States

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Bristol, Connecticut, 06010, United States

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Danbury, Connecticut, 06810, United States

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Boynton Beach, Florida, 33426, United States

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Coral Springs, Florida, 33071, United States

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Hialeah, Florida, 33012, United States

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Homestead, Florida, 33030, United States

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Largo, Florida, 33777, United States

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Miami, Florida, 33165, United States

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Orlando, Florida, 32803, United States

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Orlando, Florida, 32806, United States

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Orlando, Florida, 32825, United States

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Plant City, Florida, 33563, United States

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Winter Haven, Florida, 33880, United States

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Winter Park, Florida, 32789, United States

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Atlanta, Georgia, 30342, United States

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Columbus, Georgia, 31909, United States

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Urbana, Illinois, 61801, United States

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Evansville, Indiana, 47714, United States

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Indianapolis, Indiana, 46202, United States

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Pratt, Kansas, 67124, United States

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Madisonville, Kentucky, 42431, United States

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Chevy Chase, Maryland, 20815, United States

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Towson, Maryland, 21204, United States

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Marlborough, Massachusetts, 01752, United States

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Ann Arbor, Michigan, 48109, United States

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Chesterfield, Michigan, 48047, United States

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Troy, Michigan, 48098, United States

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Jackson, Mississippi, 39202, United States

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Mexico, Missouri, 65265, United States

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Reno, Nevada, 89511, United States

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Marlton, New Jersey, 08053, United States

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Teaneck, New Jersey, 07666, United States

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Brooklyn, New York, 11235, United States

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Flushing, New York, 11355, United States

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Great Neck, New York, 11021, United States

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New York, New York, 10016, United States

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Poughkeepsie, New York, 12601, United States

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Chapel Hill, North Carolina, 27599, United States

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Jacksonville, North Carolina, 28546, United States

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Kinston, North Carolina, 28501, United States

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Raleigh, North Carolina, 27612, United States

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Salisbury, North Carolina, 28144, United States

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Mentor, Ohio, 44060, United States

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Oklahoma City, Oklahoma, 73104, United States

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Sayre, Pennsylvania, 18840, United States

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Charleston, South Carolina, 29406, United States

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Greenville, South Carolina, 29615, United States

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Orangeburg, South Carolina, 29118, United States

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Sioux Falls, South Dakota, 57108, United States

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Kingsport, Tennessee, 37660, United States

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Nashville, Tennessee, 37211, United States

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Arlington, Texas, 76012, United States

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Fort Worth, Texas, 76104, United States

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Pasadena, Texas, 77505, United States

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Southlake, Texas, 76092, United States

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Clinton, Utah, 84015, United States

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Leesburg, Virginia, 20176, United States

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Bellevue, Washington, 98004, United States

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Madison, Wisconsin, 53705-2281, United States

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MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

The study was terminated early due to difficulty in enrollment and lack of clinical study drug access. The efficacy results are not considered definitive and are considered for exploratory purposes only.

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Bausch Health Americas, Inc.

lindsey.mathew@bauschhealth.com

908-927-0873

Study Officials

• Lindsey Mathew

  Bausch Health Americas, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 15, 2014
• Study Start: August 21, 2014
• Primary Completion: August 16, 2017
• Study Completion: August 16, 2017
• Last Updated: September 10, 2019
• Results First Posted: September 10, 2019

Record last verified: 2019-09

Locations

US (72)