E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bile acid malabsoprtion is a disease in which there is a large spill-over of bileacids to the larger intestines. This causes watery diarrheas and abdominal symptoms. |
Galdesyremalabsorption er en sygdom, hvos der er mere galdesyre i tarmsystemet end hos raske individer. Dette giver vandige diarrere og abdominale gener |
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E.1.1.1 | Medical condition in easily understood language |
Bile acid malabsoprtion is a disease in which there is a large spill-over of bileacids to the larger intestines. This causes watery diarrheas and abdominal symptoms. |
Galdesyremalabsorption er en sygdom, hvos der er mere galdesyre i tarmsystemet end hos raske individer. Dette giver vandige diarrere og abdominale gener |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
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 | 10080051 |
E.1.2 | Term | Bile acid diarrhoea |
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 examine the influence of liraglutide on individuals suffering from bile acid malabsorption (BAM), in a randomised double-blinded, double dummy parallel Group non-inferiority study.
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Studiets formål er at undersøge liraglutids virkning på individer der lider af galdesyremalabsorption i et randomiseret, dobbelt blinded, double dummy, non-inferiør med parallelle grupper studie.
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E.2.2 | Secondary objectives of the trial |
Not applicable |
ikke anvendelig |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Caucasian ethnicity • SeHCAT-verified moderate (5–10% bile acid retention after 7 days) or severe type 2 BAM (<5% retention) • Normal haemoglobin (for men 8.3-10.5 mmol/L; for women 7.3-9.5 mmol/L) • Age above 18 years and below 75 years • Informed and written consent • BMI >18,5 kg/m2 and <40 kg/m2 • Glycated haemoglobin (HbA1c) <48 mmol/mol
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• Kaukasisk etnicitet • SeHCAT verificeret moderat til svær galdesyremalabsorption • Normal hæmoglobin (mænd 8,3-10,5 mmol/L, kvinder 7,3-9,5 mmol/L) • Alder mellem 18 og 75 år • Informeret og skriftligt samtykke • BMI mellem 18,5 og 40kg/m2 • Langtidsblodsukker (HbA1c) < 48mmol/mol
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E.4 | Principal exclusion criteria |
• History of or present hepatobiliary disorder (except for non-alcoholic steatotic liver disease) and/or alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3 times upper limit of normal) or history of hepatobiliary disorder • Gastrointestinal disease (except for BAM), previous intestinal resection or any major intra-abdominal surgery • Diabetes mellitus • Nephropathy with eGFR < 30 mL/min/1.73m2 • Treatment with medicine that cannot be paused for 12 hours • Hypothyroidism or hyperthyroidism, if not well regulated. • Treatment with oral anticoagulants • Active or recent malignant disease • Any treatment or condition requiring acute or sub-acute medical or surgical intervention • Female of child-bearing potential who is pregnant, breastfeeding or intend to become pregnant or is not using adequate contraceptive methods, which includes Intrauterine Device (IUD) og birth control pills. • Known or suspected hypersensitivity to trial products or related products • Any condition considered incompatible with participation by the investigators
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• Tidligere eller nuværende leversygdom (dog ikke non-alkoholiske steatotisk lever sygdom) og alanin aminotransferase (ALAT) og/eller aspartate aminotransferase (ASAT) forøget mere end tre gange over normale niveauer. • Mave/tarm sygdomme fraset galdesyremalabsorption, resektion af tarmen eller andre store kirurgiske indgreb i mave/tarmkanalen. • Sukkersyge • Lav nyrefunktion med eGFR < 30mL7min/1,73m2 • Behandling med medicin som ikke kan pauseres i 12 timer. • Ikke reguleret højt eller lavt stofskifte • Anti-koagulations behandling • Nylige eller aktive maligne sygdomme • Behandling eller tilstande som kræver akut eller subakut medicinsk eller kirurgisk behandling • Fertile kvinder som ikke bruger prævention i form af medicinsk behandling eller har opsat spiral (IUD) • Kendt allergi eller har mistanke om allergi overfor de medikamenter og produkter som bruges i forsøget. • Enhver tilstand som ikke findes forenelig med deltagelse af den forsøgsansvarlige læge.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point is proportion of patients experiencing response to treatment (i.e. >25% reduction in stool frequency) in the end of the 6-week intervention period; non-inferiority between the two groups. Daily symptom diaries will be used to record stool frequency. |
Det primære end point er andelen af patienter som oplever en effekt af behandlingen , fx reduktion af afføringshyppighed >25%, i de 6 ugers intervention.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be asked to record any adverse events in their symptom diaries. The symptoms diaries will be filled in on a daily basis during weeks -1, 1, 3 and 6.
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Deltagerne fører dagligt dagbog over afføringshyppighed. Dagbøgerne bliver udfyld i ugerne -1, 1, 3 og 6. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints encompass: • Stool consistency as assessed by the Bristol Stool-form Scale • Proportion of patients experiencing remission of type 2 BAM-related diarrhea (<2 formed or semi-formed stools per day) • Symptomatic relief of BAM symptoms as assessed by The Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS) and The IBS Severity Scoring System (IBS-SSS) • Proportion of patients tolerating treatment (i.e. maintaining treatment throughout the 6-week treatment period) and not tolerating treatment, respectively • Change in health-related quality of life score as assessed by SF-36v2(37). Further secondary endpoints include • Change in percent retention of bile acid (as assessed by SeHCAT) from baseline, proportions of patients 1) improving their BAM severity (from moderate BAM to normal condition or from severe BAM to moderate BAM or normal condition (as assessed by SeHCAT)), 2) experiencing no change in BAM category (as assessed by SeHCAT) and 3) experiencing deterioration in BAM category (i.e. from moderate to severe BAM as assessed by SeHCAT). Of note, SeHCAT results represent exploratory secondary endpoints as BAS treatment - in contrast to liraglutide treatment - is expected to reduce retention of bile acids. For the same reason retention of bile acid as assessed by SeHCAT cannot be used as a primary. • Fasting serum/plasma concentrations of total bile acids, fractionated bile acids, cholesterol profile, triglycerides, free fatty acids, C4 (marker of bile acid synthesis), FGF19, glucose, glycated haemoglobin A1c (HbA1c), insulin, C-peptide and glucagon. • Faecal content of bile acids and microbiota composition will be evaluated as exploratory endpoints.
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Sekundære end points er; • afføringskonsistens, ved brug af bristol stool-form scale, • andelen af deltager som oplever reduktion af type 2 galdesyrerelateret diarre • reduktion af galdesyremalabsorption-symptomer angivet på ”the gastrointestinal symptom rating scale-IBS” (GSRS-IBS) og ”the IBS severity scoring system” (IBS-SSS) • andelen af patienter som tåler og ikke tåler behandlingen • ændring i helbreds relateret ændring i livskvalitet ved SF-36v2 • Ændringer i resultater fra SeHCAT skanninger, dette vil dog ses i gruppen der behandles med aktivt colesevelam, da det forventes at sænke retentionen. • Blodprøver taget fastende, herunder totalt frie galdesyrer, fraktionerede galdesyrer, lipid profil, frie fede fedtsyrer, C4 (en markør for galdesyresyntese), FGF-19, langtidsblodsukker, insulin, C-peptid og glukagon. • Afføringsprøver mhp. analyse af galdesyrer og mikrobiotisk sammensætning
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Questionaries: week -1(baseline), 1,3,6 SeHCAT, blodsamples and faeces samples: Week -1(baseline), 3 and 6 |
Spørgeskemaer Uge -1(baseline), 1,3 og 6 SeHCAT, blodprøver og afføringsprøver: Uge -1 (baseline), 3 og 6 |
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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 | 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.8.1.7.1 | Other trial design description |
double dummy, non-inferør |
double dummy, non-inferior |
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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 | 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 | 6 |
E.8.9.1 | In the Member State concerned days | |