A Study to Assess Treatment Efficacy and Safety of Rifaximin DR Twice Daily in Subjects with Active Crohn's Disease for 52 weeks.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2014-001644-38-DE
• Date of registration: 18/09/2014
• Prospective Registration: Yes
• Primary sponsor: Salix Pharmaceuticals, Inc.
• Public title: A Study to Assess Treatment Efficacy and Safety of Rifaximin DR Twice Daily in Subjects with Active Crohn's Disease for 52 weeks.
• Scientific title: A Double-Blind, Placebo-Controlled, Parallel-Group, Multicentre, 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
• Date of first enrolment: 02/02/2015
• Target sample size: 660
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001644-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Czech Republic, France, Germany, Hungary, Israel, Poland, Russian Federation, United States

Contacts

• Name: Regulatory Affairs.
• Affiliation: Salix Pharmaceuticals, Inc

• Name: Regulatory Affairs.
• Affiliation: Salix Pharmaceuticals, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
- Subject is 18 years of age at screening.
- Subject is male or female.
- Females of childbearing (reproductive) potential must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study.
- Subject has moderate, non-fistulizing Crohn's disease in the ileum and/or colon as defined by a CDAI score of = 220 and = 450 points prior to randomization; and a SESCD score of =7. The SES-CD score will be calculated using the baseline ileocolonoscopy performed during the Screening Period.
- During the Screening Period, the subject has the following average abdominal pain and average number of liquid/very soft stools:
? An average daily score of > 1.5 for abdominal pain (from CDAI Item 2), and
? An average daily count of > 1.5 for liquid/very soft stools (from CDAI Item 1).
- Liquid/very soft stool will be defined as a consistency of Type 6 or Type 7 on the BSFS.
- Subject is capable of understanding the requirements of the study, is willing to comply with all study procedures, and demonstrates ability to comply with the study electronic systems (including access to Wi-Fi) required to record Crohn's disease symptoms and CDAI components.
- Subject understands the language of the informed consent form (ICF), and is capable and willing to sign the informed consent form.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160

Exclusion criteria:
-Subject has a diagnosis of ulcerative or indeterminate colitis.
-Subject has a diagnosis of Celiac Disease.
-Subject has had bowel surgery within 12 weeks prior to screening
and/or has surgery planned or deemed likely for Crohn's disease during the study period.
-Subject has had more than one segmental colonic resection.
-Subject has presence of an ileostomy or colostomy.
-Subject has known fixed symptomatic stenosis/stricture of the small or large bowel.
-Subject has had more than 3 small bowel resections, or symptoms associated with short bowel syndrome.
-Subject has current evidence of peritonitis.
-Subject had history or evidence of colonic mucosal dysplasia.
-Subject had history or evidence of adenomatous colonic polyps that have not been removed.
-Subject has evidence of hepatic dysfunction, viral hepatitis, or current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH) as well as liver function tests (LFTs) with values = 1.5 times the upper limit of normal (ULN) for any of the following LFTs: alanine aminotransferase (ALT), aspartate aminotransferase
(AST), alkaline phosphatase, or bilirubin at Screening.
-Subject has diabetes (Type 1 or 2) that is poorly controlled in the opinion of the investigator, or has had an HbA1c 12% within 3 months prior to Screening or at the Screening Visit
-Subject has history of the following conditions per Diagnostic and Statistical Manual of Mental Disorders, 5th edition:
a major psychiatric disorder (including major depression or psychosis) alcohol or substance abuse within 24 months prior to signing the informed consent
-Subject has a history of seizure disorders.
-Subject has renal disease manifested by elevations in serum creatinine and/or blood urea nitrogen concentrations of =1.5 times the ULN.
-Subject has unstable cardiovascular or pulmonary disease, categorized by a worsening in the disease condition that requires a change in treatment or medical care within 30 days prior to randomization.
-Subject has an active malignancy within the last 5 years.
-Subject has donated blood or blood products within the past 4 weeks prior to randomization.
-Subject has known varicella, herpes zoster, or other severe viral infection within 6 weeks of randomization.
-Subject has known human immunodeficiency virus (HIV) infection.
-Subject has a positive stool test for Yersinia enterocolitica, Campylobacter jejuni, Salmonella, Shigella, ovum and parasites, and/or Clostridium difficile.
-Subject has a history of tuberculosis infection and/or has received treatment for a tuberculosis infection. If subject has had a previous positive test for tuberculosis antigen then they must have a current negative chest X-ray to be eligible.
-Subject used any biologic within 12 weeks prior to randomization.
-Subject is unwilling to be tapered off corticosteroids by Week 8 of the Treatment Period or the subject is known by the Investigator to be steroid dependent.
-Subject used cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or similar drugs within 8 weeks prior to randomization.
-Subject used any oral or intravenous antibiotic including rifaximin, rifampin or any drugs in the rifamycin group, within 4 weeks prior to the screening visit.
-Subject had rectal administration of 5-ASA or corticosteroid enemas/foams/suppositories within 2 weeks prior to screening visit.
-Subjects used tube or enteral feeding, an elemental diet, or parenteral alimentation wit

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of active Crohn’s disease
MedDRA version: 19.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Rifaximin Delayed Release (DR)
Pharmaceutical Form: Tablet
INN or Proposed INN: RIFAXIMIN
CAS Number: 80621-81-4
Current Sponsor code: Rifaxmin DR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Between week 16 and Week 17.

Main Objective: To determine the efficacy of Rifaximin DR 800 mg BID vs. placebo for the induction of clinical remission and endoscopic
response following 16 weeks of treatment in subjects presenting with active moderate Crohn’s disease.

Secondary Objective: - To evaluate clinical and endoscopic remission following an additional 36-week Long Term Treatment Phase of Rifaximin DR 800 mg BID vs. placebo.
-Assess the safety of Rifaximin DR following a 16-week induction, and an additional 36- week Long Term Treatment Phase (i.e., up to 52 weeks of treatment for eligible subjects).
- Assess the population pharmacokinetics of Rifaximin DR.
- Characterize the gastrointestinal microbiota from stool samples, and antibiotic resistance from bacteria cultured from stool samples before and after treatment with Rifaximin DR.
- Evaluate the effects of Rifaximin DR treatment on indices of health outcomes.
- Assess the effects of Rifaximin DR treatment on biological (inflammatory) markers of disease.

Primary end point(s): - 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 rating of = 1(from CDAI Item 2) on each day for the 7 days prior to the Week 16 visit.

- 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 will be calculated from centrally-read digital video of ileocolonoscopies performed at baseline and between Week 16 and Week 17.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 52

Secondary end point(s): - 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 rating of = 1(from CDAI Item 2) on each day for the 7 days prior to the Week 52 visit.
-Endoscopic remission defined as a SES-CD score of = 2 at Week 52. SES-CD scores will be calculated from centrally-read digital video of ileocolonoscopies performed at Week 52.

Secondary ID(s)

RECD3125

2014-001644-38-HU

Source(s) of Monetary Support

Salix Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 19/07/2019
• Date Completed: 16/08/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001644-38/results