Efficacy, Safety, and Tolerability of 4-MUST Tablets in Chronic Cholecystitis and Biliary Dyskinesia

Valenta Pharm

Status and phase: Enrolling; Phase 2

Conditions: Biliary Dyskinesia; Chronic Cholecystitis

Treatments: Drug: 4-MUST; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06842966

GIB-02-03-2024

Details and patient eligibility

About

This study aims to evaluate the efficacy, safety, and tolerability of the drug 4-MUST at various doses compared to placebo in patients with chronic cholecystitis and biliary dyskinesia

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males and females aged 18-70 years.
2. Presence of established gastrointestinal diseases: Chronic cholecystitis (K81.1); Dyskinesia of the bile duct or gallbladder (K82.8).
3. Presence of pain/discomfort in the upper abdomen combined with at least one of the following symptoms: Heartburn; Belching; Nausea; Abdominal bloating; Borborygmi (stomach rumbling); Flatulence; Constipation; Diarrhea.
4. Maximum severity of pain/discomfort in the upper abdomen over the past week is 40 mm or more on the VAS (Visual Analog Scale).
5. Severity of gastrointestinal symptoms according to the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire is at least 30 points.
6. Women who are either sexually abstinent or using effective contraception methods (e.g. intrauterine devices, contraceptive patches, long-acting injectable contraceptives, or double barrier methods) for at least 8 weeks before and 3 weeks after the end of the study, with a confirmed negative pregnancy test, as well as women with documented infertility or non-childbearing status (e.g. hysterectomy, tubal ligation, infertility or menopause for more than 1 year) or men using barrier contraceptives throughout the study and for 3 weeks after its completion, or men unable to conceive (documented conditions: vasectomy, infertility).
7. Signed and dated informed consent from.

Non-inclusion Criteria:

1. Peptic ulcer disease, duodenal ulcer, erosive GERD.
2. Toxic megacolon.
3. Paralytic ileus.
4. Gilbert's syndrome.
5. Abdominal adhesion disease.
6. Blood in stool, unexplained weight loss, fever, anemia.
7. Inflammatory and erosive gastrointestinal diseases.
8. Irritable bowel syndrome, non-specific ulcerative colitis, Crohn's disease.
9. Oncological diseases of the gastrointestinal tract (including past diagnoses).
10. History of gastrointestinal surgical procedures, including but not limited to endoscopic papillotomy and cholecystectomy, exept for appendectomy.
11. Use of prohibited therapy medications within 3 days prior to randomization.
12. History of mental illnesses.
13. Chronic heart failure IIb-III stages and/or III-IV functional classes according to NYHA, angina pectoris III-IV functional classes.
14. Chronic kidney disease stage IIIa-V (according to NKF/KDOQI, 2006).
15. Established diagnosis of liver failure, including in history and/or changes in liver enzyme activity: Increase in AST, ALT, ALP and/or γ-GTP more than 3 times above the upper limit of normal; Increase in total bilirubin more than 2 times above the upper limit of normal or development of jaundice.
16. HIV, syphilis, viral hepatitis B or C, including in history.
17. Lactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome.
18. Liver cirrhosis.
19. Hypersensitivity to the active ingridient or any of the excipients of the drug 4-MUST.
20. Severe, decompensated or unstable somatic diseases (any diseases or conditions that threaten the patient's life or worsen their prognosis and make it impossible for the patient to participate in clinical research).
21. Diabetes mellitus in a state of subcompensation and decompensation.
22. Systemic connective tissue diseases.
23. Autoimmune diseases.
24. Need for surgical and/or endovascular treatment and/or necessity for hemodialysis procedures.
25. Epilepsy or seizures of unclear etiology, including in history.
26. Alcoholism, substance abuse or drug addiction, including in history.
27. Uncorrected electrolyte disturbances.
28. History of surgery within 6 month prior to screening.
29. Women during pregnancy or lactation; women planning to become pregnant within the next 6 months.
30. Patients who require prohibited concomitant therapy within this study framework.
31. Participation in another clinical trial within the last 3 months prior to the screening visit date.
32. Lack of willingness to cooperate from the patient's side.
33. Other conditions that, in the investigator's judgement, may preclude the patient's participation in the study.

Exclusion criteria

1. Incorrect enrollment of a patient in the study (failure to meet inclusion/exclusion criteria at the time of randomization).
2. Ineffectiveness of therapy. The therapy will be deemed ineffective if there is no clinical improvement by visit 3 (15±1 days of therapy) - persistence or increase in the severity of pain/discomfort in the upper abdomen on the VAS compared to baseline. If excluded, the patient will be assigned alternative treatment at the discretion of the investigator.
3. Patient non-compliance (a compliant patient is defined as one who has taken at least 202 and no more than 303 tablets).
4. Requirement for prohibited concomitant therapy.
5. If the investigator judges that comtinued participation in the study would harm the patient.
6. Pregnancy or the need for breastfeeding in the patient.
7. Gross violation by the patient of the study protocol procedures outlined in the patient information sheet (PIS).
8. Withdrawal of informed consent (patient's unwillingness to continue participation in the study).
9. Loss of contact with the patient (inability to reach the patient via mobile and home phone (if applicable), as well as through a contact person; there must be at least three documented attempts to contact the patient).
10. Emergence during the study of any diseases or conditions that worsen the patient's prognosis, making it impossible for the patient to continue participating in this clinical trial.
11. Any other reasons, including administrative issues, that in the investigator's judgement may interfere with subject's ability to comlete the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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300 participants in 4 patient groups, including a placebo group

4-MUST, 128 mg

Experimental group

Description:

Patients will receive 1 tablet of the drug 4-MUST (128 mg of trimebutine 4-methylumbelliferyl sulfate) and 2 placebo tablets three times a day.

Treatment:

Drug: Placebo

Drug: 4-MUST

4-MUST, 256 mg

Experimental group

Description:

Patients will receive 2 tablets of the drug 4-MUST (256 mg of trimebutine 4-methylumbelliferyl sulfate) and 1 placebo tablet three times a day.

Treatment:

Drug: Placebo

Drug: 4-MUST

4-MUST, 384 mg

Experimental group

Description:

Patients will receive 3 tablets of the drug 4-MUST (384 mg of trimebutine 4-methylumbelliferyl sulfate) three times a day.

Treatment:

Drug: 4-MUST

Placebo

Placebo Comparator group

Description:

Patients will receive 3 placebo tablets three times a day.

Treatment:

Drug: Placebo