Placebo Controlled Study of 3 Doses of Rifaximin-EIR Tablet to Treat Moderate, Active Crohn's Disease

Study Overview
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Brief Summary
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This study aims to determine which of 3 doses of a non-absorbable antibiotic Rifaximin is most effective in treating active moderate Crohn's disease. Rifaximin tablets are already marketed in some European countries and the USA to treat traveller's diarrhoea. A new gastro-resistant form of Rifaximin called Rifaximin-Extended Intestinal Release (EIR) will be used in this study. These tablets dissolve in the stomach,releasing gastro-resistant granules which pass into the intestines and deliver Rifaximin directly to the site of the disease. Rifaximin is not absorbed, making it more effective and greatly reducing the frequency of side effects.

Official Title
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A Phase II, Multicentre, Double-blind, Randomised, Dose Range Finding Placebo Controlled Study of Rifaximin-EIR Tablet: Clinical Effectiveness and Tolerability in the Treatment of Moderate, Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Rifaximin-EIR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of Crohn's disease localised in the ileum and/or colon, documented either radiologically or endoscopically at least 3 months previously; patients with a CDAI of ≥ 220 to ≤ 400; patients capable of and willing to conform to the study protocol; patients who have provided signed and dated written informed consent. Exclusion Criteria: patients potentially needing immediate surgery for Crohn's disease, including patients with occlusive symptoms and/or stenotic tract with dilation above; patients with active perianal Crohn's disease; patients with other infectious, ischemic, or immunological diseases with gastrointestinal involvement; patients with symptoms attributed to Short Bowel Syndrome or previous surgery; patients with stoma; patients affected by upper gastro-intestinal disease (gastro-duodenum-jejunum Crohn's disease) alone or in combination with colitis or ileitis; patients treated with: oral steroids and budesonide less than 30 days prior to screening; i.v. steroids less than 30 days prior to screening; antibiotics (such as metronidazole, tinidazole, ciprofloxacin, clarithromycin) less than 15 days prior to screening; rectal steroids less than 30 days prior to the screening visit; anti-tumour necrosis factor (anti-TNF) and other biological therapies less than 6 months prior to the screening visit; pregnant women or nursing mothers; females of childbearing age (unless surgically sterile) without a negative urine pregnancy test at screening and at enrolment; patients with severe hepatic insufficiency (Child C); patients with severe cardiac insufficiency (NYHA - New York Heart Association classes 3 - 4); patients with known hypersensitivity to Rifaximin; any condition or circumstance that would prevent completion of the study or interfere with analysis of study results, including a history of drug or alcohol abuse, mental illness or non-compliance with treatments or visits, with immunological (including HIV infection), haematological or neoplastic disease; withdrawal of informed consent; patients who have used any investigational drug (except biological therapies) within 3 months prior to screening; patients who have donated 250 ml or more of blood in the last 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Rifaximin-EIR tablet 1x400 mg + Placebo 2 tablets bid | Drug: Rifaximin-EIR<br>* Comparison of 800 mg, 1600 mg and 2400 mg Rifaximin-EIR versus placebo in the treatment of active moderate Crohn's disease<br>* Other names: GRACE;|
| Experimental: B<br>Rifaximin-EIR tablet 2x400 mg + Placebo 1 tablet bid | Drug: Rifaximin-EIR<br>* Comparison of 800 mg, 1600 mg and 2400 mg Rifaximin-EIR versus placebo in the treatment of active moderate Crohn's disease<br>* Other names: GRACE;|
| Experimental: C<br>Rifaximin-EIR tablet 3x400 mg bid | Drug: Rifaximin-EIR<br>* Comparison of 800 mg, 1600 mg and 2400 mg Rifaximin-EIR versus placebo in the treatment of active moderate Crohn's disease<br>* Other names: GRACE;|
| Placebo Comparator: D<br>Placebo 3 tablets bid | Drug: Rifaximin-EIR<br>* Comparison of 800 mg, 1600 mg and 2400 mg Rifaximin-EIR versus placebo in the treatment of active moderate Crohn's disease<br>* Other names: GRACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission (Crohn's Disease Activity Index < 150 points) |  | After 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response (reduction of baseline CDAI score by 100 points or more) |  | Any time during the 12 weeks of treament | 
| Clinical response (reduction of baseline CDAI by 70 points or more) |  | At any time during the 12 weeks of treatment | 
| Time to obtain clinical response and remission |  | During the 12 weeks of treatment | 
| Maintenance of clinical remission |  | 2 weeks after the end of the 12 weeks of treatment | 
| Maintenance of clinical remission |  | 12 weeks after the end of the 12 weeks of treatment | 
| Number of treatment failures |  | During the 12 weeks of treatment | 
| Definition of therapeutic dose to be used in subsequent phase III trials. |  | After statistical analysis of the results | 
| Adverse events |  | Throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rifaximin-EIR, Crohn's disease, remission