Authorised Therapeutic exploratory (Phase II) Bile acid diarrhoea

Efficacy and safety of a novel dual pH-dependent delayed-release ColeseveLam for the trEatment of bile Acid diarrhoea: a Randomized, double-blind, parallel-group, placebo-controlled clinical trial – CLEAR

EU CTIS ID: 2025-523868-20-00

What this study is testing

Primary efficacy objective: To demonstrate the superiority of a 12-day treatment with dual pH-dependent delayed-release colesevelam vs. placebo in BAD remission rate for participants with moderate-to-severe BAD, as defined by 75SeHCAT diagnostic criteria.

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Signed written informed consent.
2. Male or female, age ≥ 18 and < 80 years.
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).
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).
5. Willingness and capability to fulfil all tasks foreseen by the trial protocol.
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.

You likely can't join if

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).
10. History of acute myocardial infarction, or stable or unstable angina.
11. History of stroke or transient ischemic attack within 6 months prior to Visit 1.
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.
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.
14. Fasting triglycerides level above 3.4 mmol/L (300.9 mg/dL) at Visit 1.

See the full eligibility criteria

Who can join

1. Signed written informed consent.
2. Male or female, age ≥ 18 and < 80 years.
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).
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).
5. Willingness and capability to fulfil all tasks foreseen by the trial protocol.
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.

What rules you out

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).
10. History of acute myocardial infarction, or stable or unstable angina.
11. History of stroke or transient ischemic attack within 6 months prior to Visit 1.
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.
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.
14. Fasting triglycerides level above 3.4 mmol/L (300.9 mg/dL) at Visit 1.
15. History of or known allergy or hypersensitivity or intolerance to colesevelam or its excipients.
16. History of or known allergy to 75SeHCAT or its excipients.
17. Prior and concomitant treatment with bile acid sequestrants (i.e., cholestyramine, colestipol, colesevelam) starting from 1 week prior to Visit 1.
18. Previous unsuccessful treatment of BAD with colesevelam.
19. Current treatment with oral anticoagulants, including warfarin and new oral anticoagulants.
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.
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.
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, antispasmodics are allowed to manage pain during the post-treatment follow-
22. Prior and concomitant rectal treatments (other than topical steroids for the treatment of haemorrhoids) starting from 2 weeks before Visit 1.
23. Prior and concomitant treatment with antibiotics starting from 2 weeks before Visit 1.
24. Prior and concomitant treatment with immunosuppressant or immunomodulator agents including monoclonal antibodies starting from 6 weeks prior to Visit 1.
25. Prior and concomitant treatment with cyclosporine starting from 2 months before Visit 1.
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).
27. Concomitant use of statins or fenofibrate.
28. History of drug abuse or use of illegal drugs.
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).
3. Known or suspected bowel (subileus or ileus) or biliary duct obstruction.
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).
31. Pregnancy or breastfeeding throughout the whole trial duration.
4. Known or suspected dysphagia.
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).
6. Acute suspected or proven viral gastroenteritis within 4 weeks prior to Visit 1.
7. Acute suspected or proven non-viral gastroenteritis within 8 weeks prior to Visit 1.
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.
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.

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.