Efficacy, Safety, and Tolerability of 4-MUST, 128 mg Tablets in Chronic Cholecystitis and Biliary Dyskinesia

Inclusion Criteria44

• Males and females aged 18-70 years.
• Diagnosed with chronic cholecystitis (K81.1) and/or dyskinesia of the cystic duct or gallbladder (K82.8) prior to enrollment; diagnosis supported by clinical history of exacerbations and remissions and/or imaging/laboratory findings.
• Upper abdominal pain or discomfort attributable to gallbladder or biliary tract dysfunction (per investigator assessment), accompanied by ≥1 of the following: heartburn, belching, nausea, abdominal bloating, borborygmi (stomach rumbling), flatulence, constipation, or diarrhea.
• Maximum severity of pain/discomfort in the upper abdomen over the past week is 40 mm or more on the VAS (Visual Analog Scale).
• Severity of gastrointestinal symptoms according to the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire is at least 30 points.
• The total bilirubin level does not exceed 2 times the upper limit of normal (no more than 42 μmol/L).
• 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).
• Signed and dated informed consent from.
• Gastric or duodenal ulcer, erosive gastroesophageal reflux disease (GERD), or other inflammatory/erosive gastrointestinal diseases in the acute stage, unless stable remission for ≥ 1 year since the last exacerbation.
• Indication for surgical or endoscopic intervention due to exacerbation of chronic cholecystitis or complications of biliary tract dyskinesia.
• Toxic megacolon.
• Paralytic ileus.
• Gilbert's syndrome.
• Choledocholithiasis (or a high risk of its development, as determined by the investigator);
• Impaired bile outflow due to adhesions in the abdominal cavity.Abdominal adhesion disease.
• Irritable bowel syndrome, non-specific ulcerative colitis, Crohn's disease.
• Gastrointestinal malignancy (including history of) or suspected gastrointestinal malignancy (e.g., blood in stool, unexplained weight loss, fever, anemia).
• Any other oncological diseases known at the time of screening, or suspicion thereof.
• History of gastrointestinal surgery, including cholecystectomy or endoscopic sphincterotomy (appendectomy excluded).
• Use of prohibited therapy medications within 3 days prior to randomization.
• History of mental illnesses.
• Chronic heart failure IIb-III stages and/or III-IV functional classes according to NYHA, angina pectoris III-IV functional classes.
• Chronic kidney disease stage IIIa-V (according to NKF/KDOQI, 2006).
• History of or current hepatic impairment; or liver test abnormalities: AST, ALT, ALP, or GGT >3 above the upper limit of normal (ULN); total bilirubin >2 ULN or clinical jaundice.
• HIV, syphilis, viral hepatitis B or C, including in history.
• Lactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome.
• Liver cirrhosis.
• Hypersensitivity to the active ingridient or any of the excipients of the drug 4-MUST.
• Severe, decompensated, or unstable somatic conditions that are life-threatening, worsen prognosis, or preclude safe study participation.
• Diabetes mellitus in a state of subcompensation and decompensation.
• Systemic connective tissue diseases.
• Autoimmune diseases.
• Indication for hemodialysis procedures.
• Epilepsy or seizures of unclear etiology, including in history.
• Alcoholism, substance abuse or drug addiction, including in history.
• Uncorrected electrolyte disturbances.
• QTcF interval on a 12-lead electrocardiogram (ECG) ≥430 ms in men and ≥450 ms in women.
• Episodes of constipation during the last 3 months that required the prescription of drug therapy.
• History of surgery within 6 month prior to screening.
• Women during pregnancy or lactation; women planning to become pregnant within the next 6 months.
• Patients who require prohibited concomitant therapy within this study framework.
• Participation in another clinical trial within the last 3 months prior to the screening visit date.
• Unwillingness or inability to comply with study procedures and protocol requirements..
• Other conditions that, in the investigator's judgement, may preclude the patient's participation in the study.