NCT02240121

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

Terminated Phase 3 Results posted Last updated 10 September 2019

What this trial tests

Phase 3 trial testing Rifaximin EIR in Crohn's Disease in 80 participants. Terminated before completion.

Timeline

21 August 2014

Primary endpoint
16 August 2017

16 August 2017

Quick facts

Lead sponsor	Bausch Health Americas, Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	80
Start date	21 August 2014
Primary completion	16 August 2017
Estimated completion	16 August 2017
Sites	72 locations across United States

Drugs / interventions tested

• Rifaximin EIR — full drug profile →
• Placebo

Conditions studied

• Crohn's Disease — all drugs for Crohn's Disease →

Sponsor

Bausch Health Americas, Inc. — full company profile →

Who can join

18 and older, any sex, with Crohn's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 16 Primary · 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.

Group	Value	95% CI
Rifaximin EIR 800 mg	9
Placebo	9

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at Week 16 Primary · 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 seve

Group	Value	95% CI
Rifaximin EIR 800 mg	18
Placebo	20

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 16 Primary · 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 ma

Group	Value	95% CI
Rifaximin EIR 800 mg	6
Placebo	6

Number of Participants With Endoscopic Response Between Week 16 and 17 Primary · Baseline, Week 16 to 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

Group	Value	95% CI
Rifaximin EIR 800 mg	16
Placebo	16

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 52 Primary · 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.

Group	Value	95% CI
Rifaximin EIR 800 mg	8
Placebo	5

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at Week 52 Primary · 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 seve

Group	Value	95% CI
Rifaximin EIR 800 mg	16
Placebo	13

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 52 Primary · 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 ma

Group	Value	95% CI
Rifaximin EIR 800 mg	7
Placebo	5

Number of Participants With Endoscopic Response at Week 52 Primary · Baseline, 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, transver

Group	Value	95% CI
Rifaximin EIR 800 mg	11
Placebo	10

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

Group	Value	95% CI
Rifaximin EIR 800 mg	12
Placebo	15

Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) Over Time Secondary · From Baseline to Week 52

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 inc

Group	Value	95% CI
Rifaximin EIR 800 mg	2
Placebo	0

Number of Participants With SES-CD Score of 0 at Week 52 Secondary · 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.

Group	Value	95% CI
Rifaximin EIR 800 mg	2
Placebo	3

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were reported from time of signing informed consent until the end of the follow-up period (2 weeks after last treatment [Week 54]) .. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rifaximin EIR 800 mg

Serious: 7/40 (18%)

Deaths: 0/40

Placebo

Serious: 7/40 (18%)

Deaths: 0/40

Serious adverse events (18 terms)

Reaction	System	Rifaximin EIR 800 mg	Placebo
Crohn's disease	Gastrointestinal disorders	—	—
Lymphadenopathy mediastinal	Blood and lymphatic system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Anal fistula	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Anal abscess	Infections and infestations	—	—
Clostridium difficile infection	Infections and infestations	—	—
Perirectal abscess	Infections and infestations	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Metastases to adrenals	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	—	—
Cholecystectomy	Surgical and medical procedures	—	—
Hypertension	Vascular disorders	—	—
Ileus paralytic	Gastrointestinal disorders	—	—

Other adverse events (30 terms — click to expand)

Reaction	System	Rifaximin EIR 800 mg	Placebo
Crohn's disease	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Pyrexia	General disorders	—	—
Bronchitis	Infections and infestations	—	—
Gastroenteritis	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Vertigo positional	Ear and labyrinth disorders	—	—
Haemorrhoids	Gastrointestinal disorders	—	—
Clostridium difficile infection	Infections and infestations	—	—
Cystitis	Infections and infestations	—	—
Folliculitis	Infections and infestations	—	—
Hordeolum	Infections and infestations	—	—
Arthropod bite	Injury, poisoning and procedural complications	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Depression	Psychiatric disorders	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—

Most-reported serious reactions: Crohn's disease, Lymphadenopathy mediastinal, Abdominal pain, Anal fistula, Nausea, Small intestinal obstruction, Vomiting, Pyrexia.

Data from ClinicalTrials.gov NCT02240121 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases.
   Oka A, Sartor RB. · · 2020 · cited 126× · PMID 32006212 · DOI 10.1007/s10620-020-06090-z