COLESEVELAM HYDROCHLORIDE for Bile acid diarrhoea

Inclusion criteria

• {"criterion_text":"- 01. Informed consent: signed written informed consent before inclusion in the study;"}
• {"criterion_text":"- 02. Sex and age: men/women, ≥18 years old inclusive;"}
• {"criterion_text":"- 03. Diagnosis or symptoms of bile acid diarrhoea: suspected or diagnosed 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, and subjects with a ≥6-month-old cholecystectomy, who fulfil the following criteria (both a. and b. conditions must be fulfilled): a1. have a fasting serum 7αC4 >46.0 ng/mL; or a2. positive SeHCAT test (SeHCAT<10%) (performed within the last 18 months before screening) independently of the 7αC4 fasting serum value; or a3. positive SeHCAT test (SeHCAT<10%) (performed more than 18 months but within the last 6 years before screening) and fasting serum value 7αC4 ≥ 31 ng/mL; or a4. fasting serum 7αC4 ≥ 31 ng/mL and ≤ 46 ng/mL, with a daily number of watery stools (Type 6 or 7 in the 7-point BSFS) more than 1 per day over 7 days; AND b. 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."}
• {"criterion_text":"- 04. Contraception (women only): women of childbearing potential must use at least one of the following highly effective methods of contraception: a. Hormonal combined oral, intravaginal, or transdermal, contraceptives for at least 2 months before the screening visit b. Progestogen-only hormonal oral, implantable, or injectable contraceptives for at least 2 months before the screening visit c. A non-hormonal intrauterine device [IUD] or an intrauterine hormone-releasing system (IUS) for at least 2 months before the screening visit d. Bilateral tubal occlusion e. A sterile sexual partner f. 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 postmenopausal 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;"}
• {"criterion_text":"- 05. 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;"}
• {"criterion_text":"- 06. Compliance with baseline diary entry: a minimum of 4 consecutive or non-consecutive days of completed diary entries within a 7-day period are necessary (except for participants fulfilling criterion 3 a4 who must have at least 7 consecutive diary entries within a 7-day period)."}

Exclusion criteria

• {"criterion_text":"- 01. Prior and concomitant gastrointestinal diseases: a) Current or recurrent disease that could affect the ileum and the enterohepatic circulation of bile acids, including ileal resection or bypass, short bowel syndrome, radiation enteritis, chronic pancreatitis, known small intestine bacterial overgrowth; b) Cholecystectomy within 6 months prior to the screening visit; c) Inflammatory bowel disease, including known microscopic colitis; d) Bowel obstruction; e) Biliary obstruction; f) Acute suspected or proven infectious (viral or bacterial) gastroenteritis within the 8 weeks prior to screening; g) Acute suspected or proven gastroenteritis within the 8 weeks prior to screening; h) Positive for Clostridium difficile toxins as detected by appropriate specific test; i) Coeliac disease, if any of the followings apply: Positive coeliac serology (e.g., anti-tissue transglutaminase [anti-TTG] IgA or equivalent) without a confirmed prior diagnosis of coeliac disease, unless false positive determined by the investigator; Diagnosis of coeliac disease within 6 months prior to the screening visit; Known or suspected non-adherence to a gluten-free diet, based on clinical assessment or patient history; Persistent gastrointestinal symptoms or abnormal laboratory findings (e.g., elevated anti-TTG, iron deficiency, or abnormal inflammatory markers) suggestive of ongoing disease activity. Participants with prior diagnosis (i.e. made > 6 months prior to screening), who are on a strict gluten-free diet for ≥ 6 months with no recent (within 6 months) dietary lapses or gluten reintroduction, have no on-going coeliac disease-related symptoms, and have no abnormal serologic or histologic laboratory findings suggestive of active disease, may be included. A positive serology can also be considered provided they are false positive confirmed by the investigator. j) Current or recurrent diseases that could affect the colon including diverticulitis, collagenous colitis, colonic resection, toxic megacolon, fistula, perforation or abscess;"}
• {"criterion_text":"- 10. Physical findings: clinically relevant abnormal physical findings which could interfere with the objectives of the study."}
• {"criterion_text":"- 02. Prior and concomitant diseases other than gastroenteric: a) Fasting triglycerides level above 3.4 mmol/L (300.9 mg/dL); b) Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness; c) 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; d) History of malignancy within the last 5 years prior to screening, with the following exception: localized malignancies that were completely resected, do not require on-going treatment, and have been in complete remission for at least 3 years prior to screening. e) Hyperthyroidism;"}
• {"criterion_text":"- 03. 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;"}
• {"criterion_text":"- 04. Prior and concomitant treatments (not to be discontinued solely due to participation in the trial): a) Treatment with other bile acid sequestrants must be stopped within 3 days before screening; b) Treatment with glucagon like peptide (GLP)-1 or GLP-2 receptor agonists (e.g., liraglutide) within 4 weeks before screening; c) Treatment with cyclosporine within 1 month before screening; d) Any concomitant medication, which colesevelam may have an interaction with, whose administration cannot be suspended for the duration of the study and which cannot be administered separated from the study drug (at least 4 h prior to or after the administration of colesevelam); e) Any concomitant medication for diarrhoea-predominant irritable bowel syndrome within 1 week prior to screening; f) Treatment with antidiarrheal drugs except loperamide (which is not permitted in the 48 hours prior to screening; g) Treatment with drugs with a known pharmacological activity on 5-hydroxytryptamine (5-HT)4, 5-HT2b or 5-HT3 receptors (e.g., tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine cilansetron, alosetron) within 2 weeks before screening; h) Treatment with drugs affecting the function of the gastrointestinal tract, including opioids (e.g. morphine, oxycodone, codeine, methadone, fentanyl, tramadol) unless taken at a stable dose for at least 4 weeks prior to screening and maintained unchanged throughout the study, anticholinergic drugs (e.g., dicyclomine, hyoscyamine, propantheline), anti-nausea drugs (e.g. trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine), laxative drugs (e.g. lactulose, sorbitol or polyethylene glycol preparations), prokinetic drugs (e.g. cisapride, metoclopramide, prucalopride, domperidone) within 4 weeks before screening; i) Rectal treatments (other than topical steroids for the treatment of haemorrhoids) within 2 weeks before screening; J) Treatment with immunosuppressant or immunomodulator agents including monoclonal antibodies (for instance, infliximab, adalimumab, azathioprine, 6-mercaptopurine, cyclosporine, vedolizumab, tofacitinib, filgotinib, ozanimod, etc.), within 4 weeks prior to screening; k) Treatment with ustekinumab within 16 weeks prior to screening (due to its longer half-life compared other Disease Modifying AntiRheumatic Drugs - DMARD); l) Treatment with antibiotics within 2 weeks before screening; m) Treatment with non-steroidal anti-inflammatory drugs (e.g. aspirin or ibuprofen) within 7 days prior to screening. Prophylactic use of a stable dose of aspirin up to 100 mg/day for cardiac disease is permitted;"}
• {"criterion_text":"- 05. Inflammatory markers: C-reactive protein >1.0 mg/dL, abnormal faecal calprotectin >100 µg/g; (if considered clinically significant by the Investigator as indicating an active inflammatory, infectious, or systemic condition that may interfere with patient safety or BAD assessment);"}
• {"criterion_text":"- 06. 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;"}
• {"criterion_text":"- 07. 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;"}
• {"criterion_text":"- 08. Liver function: chronic liver disease (including primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, chronic viral hepatitis, or cirrhosis of any aetiology) 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, with the following exceptions: Participants with metabolic-associated fatty liver disease (MAFLD previously NAFLD) without evidence of advanced fibrosis may be enrolled if liver function is stable and no other exclusion applies; Isolated indirect hyperbilirubinemia (e.g., consistent with Gilbert’s syndrome) is not exclusionary if other liver function parameters are within specified protocol limits and the participant is clinically stable."}
• {"criterion_text":"- 09. Investigative drug trials: participation in experimental therapeutic trials in the last 3 months before screening;"}

Primary endpoints

• {"endpoint_text":"- Proportion of study participants, who are stool consistency responders at Week 8 after T1 or T2 as compared to 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 that has a consistency of Type 6 or 7 in the 7-point Bristol Stool Form Scale (BSFS) compared with baseline.","definition_or_measurement_approach":"Stool consistency responder defined as ≥50% reduction in the number of days with at least one stool of Type 6 or 7 in the 7-point BSFS compared with baseline; assessed at Week 8 after treatment (T1 or T2) versus placebo (P)."}

Secondary endpoints

• {"endpoint_text":"- 01. Proportion of study participants, who are stool consistency responders at Week 2 and 4 after T1 or T2 as compared to P.","definition_or_measurement_approach":"Stool consistency responder assessed at Week 2 and Week 4 (same responder definition as primary: ≥50% reduction in days with at least one Type 6 or 7 stool vs baseline)."}
• {"endpoint_text":"- 02. Proportion of study participants achieving remission of diarrhoea as per Hjortswang criteria, defined as <3 bowel movements per day and <1 stool per day with consistency of Type 6 or 7 in the 7-point BSFS calculated as the mean of the last 7 days prior to Week 8 after T1 or T2 as compared to P.","definition_or_measurement_approach":"Remission per Hjortswang criteria: mean of last 7 days prior to Week 8 with <3 bowel movements/day and <1 stool/day of Type 6 or 7 in BSFS."}
• {"endpoint_text":"- 03. Proportion of study participants, who are stool frequency responders at Week 8 after T1 or T2 as compared to P. A stool frequency responder is defined as a participant, who experiences a ≥50% reduction in the number of days with ≥3 bowel movements compared with baseline","definition_or_measurement_approach":"Stool frequency responder = ≥50% reduction in number of days with ≥3 bowel movements vs baseline; assessed at Week 8."}
• {"endpoint_text":"- 04. Proportion of study participants who achieve remission in urgency, defined as a score of <3 in the urgency numerical rating scale at Week 2, 4 and 8 after treatment with T1 or T2 as compared to P.","definition_or_measurement_approach":"Urgency remission defined as urgency numerical rating scale score <3; assessed at Weeks 2, 4 and 8."}
• {"endpoint_text":"- 05. To compare between treatments the proportion of study participants with and the number of adverse drug reactions after 8 weeks of treatment.","definition_or_measurement_approach":"Safety endpoint comparing proportion and counts of adverse drug reactions between treatment arms at 8 weeks."}
• {"endpoint_text":"- 06. Use of rescue medication (loperamide 2 mg, oral use): number and proportion of users, and amount of used rescue medication.","definition_or_measurement_approach":"Rescue medication use (loperamide 2 mg oral): number and proportion of users and amount used."}

Belgium

Earliest CTIS Part Ii Submission Date

15-04-2025

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

43

Number Of Sites

5

Number Of Participants

14

Denmark

Earliest CTIS Part Ii Submission Date

23-05-2025

Latest Decision Or Authorization Date

27-05-2025

Processing Time Days

4

Number Of Sites

3

Number Of Participants

18

Italy

Earliest CTIS Part Ii Submission Date

28-04-2025

Latest Decision Or Authorization Date

29-05-2025

Processing Time Days

31

Number Of Sites

7

Number Of Participants

50

Romania

Earliest CTIS Part Ii Submission Date

18-04-2025

Latest Decision Or Authorization Date

02-06-2025

Processing Time Days

45

Number Of Sites

4

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

14-05-2025

Latest Decision Or Authorization Date

30-05-2025

Processing Time Days

16

Number Of Sites

3

Number Of Participants

26

Primary sponsor

Full Name

Cosmo Technologies Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

Ireland

Contract research organisations

Name

Primevigilance Limited

Responsibilities

code: 8

Name

Ardena Bioanalysis B.V.

Responsibilities

code: 4

Name

Viedoc Technologies AB

Responsibilities

codes: 15 (eTMF), 3, 7

Name

1Med S.A.

Responsibilities

codes: 1, 10, 12, 2, 5, 6

Name

Anapharm Europe S.L.

Responsibilities

code: 15 (Laboratory kits management)

Name

Myonex LLC

Responsibilities

code: 14

Third parties

• {"country":"United States","full_name":"Myonex LLC","duties_or_roles":"code: 14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"UMCG","duties_or_roles":"code: 4","organisation_type":"Health care"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"codes: 15 (eTMF), 3, 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Ardena Bioanalysis B.V.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"1Med S.A.","duties_or_roles":"codes: 1, 10, 12, 2, 5, 6","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Anapharm Europe S.L.","duties_or_roles":"code: 15 (Laboratory kits management)","organisation_type":"Pharmaceutical company"}