Colesevelam hydrochloride for Bile acid diarrhoea

Inclusion criteria

• {"criterion_text":"- 1. Signed written informed consent.\n- 2. Male or female, age ≥ 18 and < 80 years.\n- 3. Evidence of moderate-to-severe BAD, as confirmed by 75SeHCAT scintigraphy (i.e., 75SeHCAT ≤10%) (during the study screening/baseline period or within two calendar years prior to Visit 1).\n- 4. Active disease according to Hjortswang criteria, i.e., symptomatic BAD, defined as follows: mean of ≥ 3 stools/day or mean of ≥ 1 watery stool (BSFS of type 6 or 7)/day over the study screening/baseline period (Days -8 to -2, i.e., the last week prior to baseline/randomization).\n- 5. Willingness and capability to fulfil all tasks foreseen by the trial protocol.\n- 6. Female of childbearing potential must have a negative urine pregnancy test (dipstick) prior to the first IMP administration, and currently using or agree to use consistently and correctly (i.e., perfect use) a highly effective method of contraception for the individual participant and her partner(s) throughout the trial and for at least one full contraceptive cycle (when applicable). Highly effective methods of contraception include the following: a) implantable progestogen-only hormone contraception associated with inhibition of ovulation; b) Intrauterine Device (IUD); c) Intrauterine Hormone-releasing System (IUS); d) combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral; intravaginal; transdermal), provided the participant has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness; e) progestogen-only hormone contraception associated with inhibition of ovulation (oral; injectable), provided the participant has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness; f) vasectomized partner, provided that the partner is the sole participant’s sexual partner and the absence of sperm has been confirmed; g) bilateral tubal occlusion or tubal ligation; h) sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the IMP (i.e., up to 24h after the end of treatment). Barrier contraceptives (i.e., diaphragm or cervical cap with spermicide and/or condoms [male or female] with or without a spermicidal agent) are not considered highly effective methods of contraception, and thus must not be used as sole method of contraception. Of note, the use of an oral contraceptive is allowed only if a properly separate administration from it of the IMP (i.e., at least four hours before or at least four hours after the oral contraceptive) can be ensured. Of note, females who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal (at least 12 months of amenorrhea following cessation of all exogenous hormonal treatment) are not considered of childbearing potential."}

Exclusion criteria

• {"criterion_text":"- 1. Ascertained organic GI diseases, including celiac disease or inflammatory bowel diseases (i.e., Crohn's Disease [CD], ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis).\n- 10. History of acute myocardial infarction, or stable or unstable angina.\n- 11. History of stroke or transient ischemic attack within 6 months prior to Visit 1.\n- 12. Clinically significant or unstable concurrent disease whose sequelae or treatment might contraindicate trial participation or interfere with the trial evaluation parameters, as judged by the Investigator.\n- 13. Any major psychiatric unstable disorder, including eating disorders, and use of antidepressant or anxiolytic agents, unless used at a stable dose for at least 6 weeks prior to baseline/randomization.\n- 14. Fasting triglycerides level above 3.4 mmol/L (300.9 mg/dL) at Visit 1.\n- 15. History of or known allergy or hypersensitivity or intolerance to colesevelam or its excipients.\n- 16. History of or known allergy to 75SeHCAT or its excipients.\n- 17. Prior and concomitant treatment with bile acid sequestrants (i.e., cholestyramine, colestipol, colesevelam) starting from 1 week prior to Visit 1.\n- 18. Previous unsuccessful treatment of BAD with colesevelam.\n- 19. Current treatment with oral anticoagulants, including warfarin and new oral anticoagulants.\n- 2. Presence of other severe GI motility disorders, or diseases that could affect the ileum and the enterohepatic circulation of bile acids or the colon, including biliary dyskinesia, gastroparesis, intestinal pseudo-obstruction, narcotic bowel syndrome, gastric and ileal resection or bypass, short bowel syndrome, radiation enteritis, chronic pancreatitis, known small intestine bacterial overgrowth, diverticulitis, collagenous colitis, colonic resection, toxic megacolon, fistula, perforation or abscess. Of note, patients who have undergone cholecystectomy are eligible for the trial.\n- 20. Current chronic treatment with drugs affecting intestinal pH (i.e., Proton Pump Inhibitors [PPIs]*, histamine H2-receptor antagonists, and antiacids) and/or altering the GI motility (i.e., drugs that act as prokinetics to stimulate GI motility, Glucagon-Like Peptide-1 (GLP-1) receptor agonists, and drugs that cause constipation or diarrhoea), as well as any modified-release or prolonged release drugs. *For PPIs, a wash-out from treatment of at least 4 weeks prior to Visit 1 is also required. Of note, concomitant probiotics are allowed if taken at a stable dosage throughout the trial.\n- 21. Concomitant use (starting from Visit 1) of laxatives or anti-diarrheal drugs, including 5-Hydroxytryptamine 3 (5􀇦HT3) receptor antagonists, such as alosetron and ondansetron, and eluxadoline (except for loperamide allowed as rescue medication starting from randomization), as well as opioids and antispasmodics for pain. Of note, antispastics are allowed to manage pain during the post-treatment follow-\n- 22. Prior and concomitant rectal treatments (other than topical steroids for the treatment of haemorrhoids) starting from 2 weeks before Visit 1.\n- 23. Prior and concomitant treatment with antibiotics starting from 2 weeks before Visit 1.\n- 24. Prior and concomitant treatment with immunosuppressant or immunomodulator agents including monoclonal antibodies starting from 6 weeks prior to Visit 1.\n- 25. Prior and concomitant treatment with cyclosporine starting from 2 months before Visit 1.\n- 26. Concomitant use of medications whose bioavailability is affected by colesevelam (i.e., olmesartan, glyburide, glimepiride, levothyroxine, anti-epileptics, ursodeoxycholic acid and oral contraceptives), except when their therapeutic regimen allows a properly separate administration of colesevelam (i.e., at least four hours before or at least four hours after such medication).\n- 27. Concomitant use of statins or fenofibrate.\n- 28. History of drug abuse or use of illegal drugs.\n- 29. Alcohol abuse, i.e., regular use of more than 2 units of alcohol per day or 10 units per week or a history of alcoholism (one unit of alcohol equals 250 ml beer, 125 ml wine or 25 ml spirits).\n- 3. Known or suspected bowel (subileus or ileus) or biliary duct obstruction.\n- 30. Participation in other clinical trials or investigations at the same time or within 90 days prior to Visit 1 (calculated from the date of the final examination of the previous study).\n- 31. Pregnancy or breastfeeding throughout the whole trial duration.\n- 4. Known or suspected dysphagia.\n- 5. Previous major abdominal surgery, including bowel ostomy (uncomplicated appendectomy, cholecystectomy, hysterectomy or caesarean section are allowed unless within 6 months prior to Visit 1).\n- 6. Acute suspected or proven viral gastroenteritis within 4 weeks prior to Visit 1.\n- 7. Acute suspected or proven non-viral gastroenteritis within 8 weeks prior to Visit 1.\n- 8. Active malignancy of any type (except for non-invasive basal or squamous cell carcinoma of the skin), or history of a malignancy other than non-invasive basal or squamous cell carcinoma of the skin. Patients with a history of malignancies that have been surgically removed with no evidence of recurrence for at least five years and no treatment prior to Visit 1 are allowed to participate in the trial.\n- 9. Patients with known (as previously documented) severe heart failure (New York Heart Association [NYHA] class IV), severe renal impairment (estimated Glomerular Filtration Rate [eGFR] <30 mL/min), or severe hepatic impairment (Child-Pugh class C) or clinically significant liver enzyme abnormality, as evidenced by elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) >3 times Upper Limit of Normal (ULN) or total direct bilirubin >2 times ULN at Visit 1."}

Primary endpoints

• {"endpoint_text":"- Primary efficacy endpoint: Proportion of participants with BAD remission, defined according to Hjortswang criteria, at the end of the stable dose treatment period (Days 6-12), considering participants with moderate-to-severe BAD defined by 75SeHCAT ≤10%.","definition_or_measurement_approach":"Defined according to Hjortswang criteria; assessed at end of stable dose treatment period (Days 6-12) in participants with moderate-to-severe BAD defined by 75SeHCAT ≤10%."}

Secondary endpoints

• {"endpoint_text":"- Secondary efficacy endopoints: Proportion of participants with BAD remission, as per Hjortswang criteria, at the end of the stable dose treatment period, considering the subgroup of participants with BAD defined by C4 >46 ng/mL.","definition_or_measurement_approach":"Proportion with remission per Hjortswang criteria at end of stable dose period, subgroup defined by C4 >46 ng/mL."}
• {"endpoint_text":"- Secondary efficacy endpoints: Change from screening/baseline period (i.e., Days -8 to -2) to stable dose treatment period (i.e., Days 6-12) in the mean number of stools/day with a BSFS type ≤2, ≥3 and ≤5, and ≥6, as self-assessed daily by participants up to End of Study (EOS) (e-diary), considering participants with BAD defined by either 75SeHCAT or C4 criteria.","definition_or_measurement_approach":"Change from Days -8 to -2 to Days 6-12 in mean number of stools/day by BSFS categories, self-assessed daily by e-diary up to EOS."}
• {"endpoint_text":"- Secondary efficacy endpoints: Change from screening/baseline period (Days -8 to -2) to stable dose treatment period (Days 6-12) in the average BSFS score, as self-assessed daily by participants up to EOS (e-diary), considering participants with BAD defined by either 75SeHCAT or C4 criteria.","definition_or_measurement_approach":"Change in average BSFS score from baseline (Days -8 to -2) to Days 6-12, self-assessed daily by e-diary up to EOS."}
• {"endpoint_text":"- Secondary efficacy endpoints: Change from screening/baseline period (Days -8 to -2) to stable dose treatment period (Days 6-12) in the mean number of stools/day (average daily frequency of defecation), as self-assessed daily by participants up to EOS (e-diary), considering participants with BAD defined by either 75SeHCAT or C4 criteria.","definition_or_measurement_approach":"Change in mean number of stools/day from baseline to Days 6-12, self-assessed daily by e-diary up to EOS."}
• {"endpoint_text":"- Secondary efficacy endpoints: Change from screening/baseline period (Days -8 to -2) to stable dose treatment period (Days 6-12) in the mean number of CSBM, defined as the spontaneous occurrence of a bowel movement associated with a feeling of complete evacuation, as self-assessed daily by participants up to EOS (e-diary), considering participants with BAD defined by either 75SeHCAT or C4 criteria.","definition_or_measurement_approach":"Change in mean number of CSBM (spontaneous bowel movement with feeling of complete evacuation) from baseline to Days 6-12, self-assessed daily by e-diary up to EOS."}
• {"endpoint_text":"- Secondary efficacy endpoints: Change from screening/baseline period (Days -8 to -2) to stable dose treatment period (Days 6-12) in the average score for urgency of defecation, as self-assessed daily by participants up to EOS, using a 7-point Likert scale (ranging from 0 to 6, where 0 = no urgency at all and 6 = a very great deal of urgency) (e-diary).","definition_or_measurement_approach":"Change in mean urgency score (7-point Likert 0-6) from baseline to Days 6-12, self-assessed daily via e-diary up to EOS."}
• {"endpoint_text":"- Secondary efficacy endpoints: Change from baseline/randomization at End of Treatment (EOT) in the average total score for the Gastrointestinal Symptom Rating Scale (GSRS), as well as the relative scores for each symptom cluster (i.e., reflux, abdominal pain, indigestion, diarrhoea and constipation) and single item, as self-assessed by participants (e-diary).","definition_or_measurement_approach":"Change in GSRS total and subscale scores from baseline to EOT, self-assessed by participants via e-diary."}
• {"endpoint_text":"- Secondary efficacy endpoints: Proportion of participants who use the rescue medication.","definition_or_measurement_approach":"Proportion of participants using rescue medication (loperamide) during study."}
• {"endpoint_text":"- Safety and tolerability endpoints: Incidence of all Adverse Events (AEs), AEs leading to IMP discontinuation, Adverse Drug Reactions (ADRs), and Serious Adverse Events (SAEs) throughout the trial.","definition_or_measurement_approach":"Incidence and characterization of AEs, AEs leading to discontinuation, ADRs and SAEs collected throughout trial."}
• {"endpoint_text":"- Safety and tolerability endpoints: Vital signs (systolic and diastolic blood pressure, and heart rate) at Visit 1, Visit 2, EOT and EOS.","definition_or_measurement_approach":"Vital signs measured at Visit 1, Visit 2, EOT and EOS (systolic/diastolic BP, heart rate)."}
• {"endpoint_text":"- Safety and tolerability endpoints: Safety laboratory evaluations at Visit 1 and EOT.","definition_or_measurement_approach":"Safety laboratory tests performed at Visit 1 and EOT."}

Other endpoints

• {"endpoint_text":"- Exploratory efficacy endpoint: Change from baseline/randomization at EOT of serum concentration of C4.","definition_or_measurement_approach":"Change in serum C4 concentration from baseline to EOT."}

Italy

Earliest CTIS Part Ii Submission Date

09-03-2026

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

24

Number Of Sites

5

Number Of Participants

50

Primary sponsor

Full Name

Monteresearch S.r.l.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Prineos S.r.l.","duties_or_roles":"Sponsor duties codes: 1,10,11,12,15 (Management of study documnetation and reporting of the clinical trial.),5","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Vi.Rel Pharma S.r.l.","duties_or_roles":"Sponsor duties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Phse S.r.l.","duties_or_roles":"Sponsor duties codes: 15 (Shipment of blood samples for serum 7α-hydroxy-4-cholesten-3-one (C4) analysis from investigational sites to centralized laboratory.)","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Advice Pharma Group S.r.l.","duties_or_roles":"Sponsor duties codes: 15 (Provider of eCRF, developer of final randomization list.)","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Karolinska Institutet","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Educational Institution"}