E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Collagenous colitis is a chronic inflammatory diarrhoeal disease. The hypothesis is that supplemental treatment wit Xifaxan can lower the risk of relapse after discontinuation of standard treatment. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048928 |
E.1.2 | Term | Colitis collagenous |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this study is to assess if 4 weeks treatment with Rifaximin as a supplement to a standard course of Budesonide against active Collagenous Colitis can reduce the risk of relapse after treatment cessation. |
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E.2.2 | Secondary objectives of the trial |
The number of patients in clinical remission 12 weeks after cessation of Budesonide in the Rifaximin group compared to the placebo group. Remission defined as < 3 daily bowel movements or < 1 watery stool per day measured as a mean during the last week. Reduction in MCDAI score from baseline to week 18. Time to relapse. Quality of life assessed by short health scale (SHS) 12 weeks after completed Budesonide-course. Number of patients in histolocigal remission 12 weeks after cessation of treatment. Changes is gut microbiome measured by 16SrDNA-analysis on stool samples. Proportion of patients in clinical remission and difference in quality of life 6 and 12 month after treatment cessation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >18 years • Written informed consent • Histological findings fulfill criteria for CC: o A thickenened subepithelial collagenous band >10 μm in veloriented colonic biopsies and o Increased count of inflammatory cells in lamina propria • Diagnostic biopsies are a maximum of two years old • A history of nonbloody, watery diarrhea for more than two weeks prior to screening in patients with recently diagnosed CC or a history of clinical relapse for more than a week in patients with known CC • Active disease: > 3 stools/day or >1 watery stool/day measured as a mean during a week prior to baseline
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E.4 | Principal exclusion criteria |
- Significant findings at colonoscopy that could cause diarrhea (colonic diverticulosis and polyps < 2 cm are not considered significant findings) - Biopsies more than two years old in a patient, who does not accept a new sigmoidoscopy - Untreated celiac disease - Positive stool cultures for pathogenic intestinal bacteria including Clostridium difficile - Suspected colitis induced by medication (diarrhea shortly after commencement of NSAID’s, statins, SSRI or PPI) - Severe comorbidity (cardiovascular, renal, endocrine, neurologic, pulmonal or psychiatric) or history of cancer during the last 5 years - Abnormal liver biochemistry (ALAT or ALP > 2,5 x upper limit), cirrhosis or portal hypertension - Pregnancy or lactation (assured by negative P-hCG at inclusion) - History of significant intestinal resection - Treatment with 5-ASA, Salazopyrin, immunomudulators (Azathioprine, 6-mercaptopurine or Methotrexate), biologic drugs (TNF-alfa-inhibitors), systemic or rectal administered glucocorticoids (except for Budesonide) within the last three month - Allergy or intolerance to Rifaximin (or similar antibiotics such as Rifampicin or Rifabutin) - Expectation of lack of cooperation or insufficient comprehension - Concomitant participation in an other clinical trial or participation within the last 30 days - Patients receiving Warfarin or Marcoumar (interaction with risk of uncontrolled INR-levels)
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of patients in clinical remission 12 weeks after cessation of Budesonide in the Rifaximin group compared to the placebo group |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Reduction in MCDAI score from baseline to week 18. Time to relapse. Quality of life assessed by short health scale (SHS) 12 weeks after completed Budesonide-course. Number of patients in histolocigal remission 12 weeks after cessation of treatment. Changes is gut microbiome measured by 16SrDNA-analysis on stool samples. Proportion of patients in clinical remission and difference in quality of life 6 and 12 month after treatment cessation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |