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

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


Eligibility Criteria:
Inclusion Criteria:

1. Men and women 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 not sexually active, or women using effective contraception methods (intrauterine devices, oral contraceptives, contraceptive patches, long-acting injectable contraceptives, double barrier methods) for 8 weeks prior to and during 3 weeks after the end of the study and have a negative pregnancy test, as well as women unable to conceive (documented conditions: hysterectomy, tubal ligation, infertility, 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. Presence of a signed and dated informed consent from the patient to participate in the study.

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 in history.
10. Surgical interventions on the gastrointestinal tract in history, including endoscopic papillotomy, cholecystectomy (excluding appendectomy).
11. Use of prohibited therapy medications within 3 days prior to randomization.
12. History of mental illnesses.
13. Presence of 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. Presence of HIV, syphilis, viral hepatitis B or C, including in history.
17. Lactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome.
18. Liver cirrhosis.
19. Increased sensitivity to active and excipient substances 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. States following surgical interventions if less than 6 months have passed since the intervention.
29. Women during pregnancy or lactation; women planning pregnancy 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 opinion of the investigator, prevent the inclusion of the patient in the study.

Exclusion Criteria:

1. Erroneous inclusion of a patient in the study (not meeting 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. Need for prohibited concomitant therapy.
5. If the investigator believes that further participation in the study would harm the patient.
6. Pregnancy of the patient, necessity for breastfeeding.
7. Gross violation by the patient of the study protocol procedures presented 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 ones, that in the investigator's opinion would prevent the subject from completing the study.