Idiopathic bile acid diarrhoea (BAD) Digestive System
Conditions
Interventions
Patients will be randomly assigned to one of the treatment schedules for 8 consecutive weeks. During the first 2 weeks, the study medication will be administered only in the evening. From Day 15 to Da
Sponsors
Cosmo Technologies Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and age: men/women, =18 years old inclusive 3. Diagnosis or symptoms of bile acid diarrhoea: suspected or diagnosed type II (idiopathic) bile acid diarrhoea or subjects presenting with symptoms compatible with bile acid diarrhoea, including subjects with suspected functional diarrhoea or IBS-D as per Rome IV criteria, who fulfil the following criteria: 3.1. Have a fasting serum 7aC4 >46.0 ng/mL 3.2. Have at least 4 days per week during the screening period with =1 bowel movement with a stool consistency of Type 6 or 7 in the 7-point BSFS 4. Contraception (women only): women of childbearing potential must use at least one of the following highly effective methods of contraception: 4.1. Hormonal combined oral, intravaginal, or transdermal, contraceptives associated with inhibition of ovulation for at least 2 months before the screening visit 4.2. Progestogen-only hormonal oral, implantable, or injectable contraceptives for at least 2 months before the screening visit 4.3. A non-hormonal intrauterine device [IUD] or an intrauterine hormone-releasing system (IUS) for at least 2 months before the screening visit 4.4. Bilateral tubal occlusion 4.5. A sterile sexual partner 4.6. True abstinence, i.e., refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject Women of non-childbearing potential or in post-menopausal status must have been in that status for at least one year. For all women of childbearing potential, serum pregnancy test result must be negative at screening; 5. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the study 6. Compliance with baseline diary entry: a minimum of 3 consecutive days of completed diary entries or 4 non-consecutive days within a 7-day period are necessary
Exclusion criteria
Exclusion criteria: 1. Prior and concomitant gastrointestinal diseases: 1.1. Current or recurrent disease that could affect the ileum and the enterohepatic circulation of bile acids, including ileal resection or bypass, short bowel syndrome, previous cholecystectomy, radiation enteritis, chronic pancreatitis, known small intestine bacterial overgrowth 1.2. Inflammatory bowel disease, including known microscopic colitis 1.3. Bowel obstruction 1.4. Biliary obstruction 1.5. Acute suspected or proven infectious (viral or bacterial) gastroenteritis within the 8 weeks prior to screening 1.6. Acute suspected or proven gastroenteritis within the 8 weeks prior to screening 1.7. Positive for Clostridium difficile as detected by appropriate specific test 1.8. Positive for coeliac disease blood test 1.9. Current or recurrent diseases that could affect the colon including diverticulitis, collagenous colitis, colonic resection, toxic megacolon, fistula, perforation or abscess 2. Prior and concomitant diseases other than gastroenteric: 2.1. Fasting triglycerides level above 3.4 mmol/L (300.9 mg/dL) 2.2. Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness 2.3. Any medical disorder that may require treatment or make the patient unlikely to fully complete the study or any condition that presents undue risk from the study medication or procedures 2.4. Malignancy in the last 5 years prior to screening 2.5. Hyperthyroidism 3. Previous unsuccessful treatments: unsuccessfully treating BAD with bile acid sequestrants (cholestyramine, colestipol or colesevelam) unless the reason for treatment failure was due to non-compliance/lack of tolerability 4. Prior and concomitant treatments (as listed in the study protocol): 5. Inflammatory markers: C-reactive protein >1.0 mg/dL; abnormal faecal calprotectin >100 µg/g 6. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations’ ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study 7. Pregnancy (women only): pregnant or lactating women or women wishing to become pregnant in the 3 months following the screening visit; positive or missing pregnancy test at screening 8. Liver function: chronic liver disease or clinically significant liver enzyme abnormality as evidenced by elevated aspartate aminotransferase, alanine aminotransferase >2.5 times upper limit of normal or total bilirubin >1.5 times upper limit of normal 9. Investigative drug trials: participation in experimental therapeutic trials in the last 3 months before screening 10. Physical findings: clinically relevant abnormal physical findings which could interfere with the objectives of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of study participants who are stool consistency responders at Week 8 after treatment with T1 or T2, compared to placebo (P). A stool consistency responder is defined as a participant who experiences a =50% reduction in the number of days with at least one stool of Type 6 or 7 consistency on the 7-point Bristol Stool Form Scale (BSFS) compared to baseline. Participants will complete a daily assessment of stool consistency using the BSFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in the proportion of stool consistency responders at Weeks 2 and 4 after T1 or T2, compared to P, assessed using the 7-point BSFS, comparing responses to baseline measurements. 2. Remission of diarrhoea at Week 8, defined according to Hjortswang criteria: fewer than 3 bowel movements per day and fewer than 1 stool per day with a consistency of Type 6 or 7 on the BSFS, calculated as the mean of the last 7 days prior to Week 8. Participants will record stool frequency (number of bowel movements) daily in a diary. Plasma levels of 7aC4 and FGF19 will also be measured at baseline and at Week 8 to support this evaluation. 3. Change in the proportion of stool frequency responders at Week 8. A stool frequency responder is defined as a participant experiencing a =50% reduction in the number of days with =3 bowel movements compared to baseline. Stool frequency will be assessed through daily diary entries recording the number of bowel movements. 4. Change in the proportion of participants achieving remission in urgency at Weeks 2, 4, and 8. Remission in urgency is defined as a score of <3 on the 11-point numerical rating scale for stool urgency. Participants will record daily stool urgency scores (0 to 10) in a diary. 5. Change in the proportion of patients experiencing adverse drug reactions after 8 weeks of treatment, assessed through diary entries and adverse event form entries recorded throughout the study period and evaluated after 8 weeks of treatment | — |
Countries
Belgium, Denmark, Italy, Romania, Spain, United Kingdom
Outcome results
None listed