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 |
diarrhoea or loose stools due to a defect in the mechanism in the terminal small bowel that should reabsorb bile acids used for digestion. In the large intestine these bile acids cause diarrhoea. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10069703 |
E.1.2 | Term | Bile acid malabsorption |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066557 |
E.1.2 | Term | Chronic diarrhoea |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
To determine the efficacy and safety of treating bile acid diarrhoea with colesevelam.
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E.2.2 | Secondary objectives of the trial |
To correlate both the current scintigraphic SeHCAT test and the biochemical markers of BAD fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) with colesevelam treatment response. this will establish clinical meaningful cut-offs and improve treatment of bile acid diarrhoea |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Validation of patient reported outcomes of quality of life |
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E.3 | Principal inclusion criteria |
• Patients with suspected bile acid diarrhoea referred for SeHCAT retention test at Holbæk, Hvidovre, Aarhus, or Aalborg university hospitals • age >= 18yo. and < 80 yo. • Women of fertile age must use safe contraception during the study as specified in the protocol • Ability to give informed consent after written and oral information in Danish language |
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E.4 | Principal exclusion criteria |
• Inflammatory bowel disease, including microscopic colitis • Investigator assessed debilitating chronic disease (WHO performance score 3-5) • Prior treatment with colesevelam • Treatment with laxatives or constipants during the study o Except for stable dose the last four weeks of psyllium husk and opioids for pain • Pregnancy • Breastfeeding women • Crucial medication that cannot be separated appropriately from colesevelam o i.e. taken one hour before or 4 hours after colesevelam. • Oral anticoagulation, both warfarin, and new oral anticoagulation • Treatment with cyclosporine within two months • Bowel obstruction (subileus or ileus) • Biliary obstruction • Short Bowel Syndrome • Bowel ostomy • Allergy to colesevelam or its constituents • Allergy to placebo constituents (excluding lactose) • Investigator assessed high risk of non-compliance • If on statin/fibrate medication, unwilling to pause medication between study visits 1 and 2 • Acute suspected or proven viral gastroenteritis within the recent 4 weeks • Acute non-viral gastroenteritis within the recent 8 weeks
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E.5 End points |
E.5.1 | Primary end point(s) |
Placebo-controlled intention to treat (ITT) diarrhoea remission rate defined by the Hjortswang criteria for colesevelam in patients with BAD defined by C4 > 46 ng/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline six days compared with the last seven of total 12 treatment days. Analysis of biobank blood samples after Last Subject Last Visit. This is expected aprox. primo 2022. |
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E.5.2 | Secondary end point(s) |
1. Per protocol (PP) analysis for the primary endpoint 2. Placebo-controlled diarrhoea ITT remission rate for colesevelam defined by the Hjortswang criteria in patients with BAD defined by SeHCAT ≤ 10% 3. Placebo-controlled diarrhoea PP remission rate for colesevelam defined by the Hjortswang criteria in patients with BAD defined by SeHCAT ≤ 10% 4. Placebo-controlled effect of colesevelam in patients with bile acid diarrhoea defined with C4 a. on the absolute number of stools (mean per day over 6 or 7 days) b. on the total number of Bristol 6 and 7 stools (mean per day over 6 or 7 days) Change in health-related quality of life assesses as the change in the total score of the Short Health Scale before vs. after |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As for the primary endpoint |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
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 | No |
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 |