Clinical trial NCT06842966: Efficacy, Safety, and Tolerability of 4-MUST Tablets in Chronic Cholecystitis and Biliary Dyskinesia
Official title: A Prospective Multicenter Randomized Double-blind Placebo-controlled Study in Parallel Groups to Evaluate the Efficacy, Safety, and Tolerability of the Drug 4-MUST, Tablets, 128 mg, When Administered at Various Doses to Patients With Chronic Cholecystitis and Biliary Dyskinesia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Cholecystitis
Biliary Dyskinesia
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2025-02-24
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Primary outcomes:
measure: Average reduction in the severity of pain/discomfort in the upper abdomen on the VAS by day 29 from the start of therapy
timeFrame: Day 29 ± 1
Secondary outcomes:
measure: Change in the total score of gastrointestinal symptom severity according to the GSRS questionnaire on days 8, 15, 22, and 29 from the start of therapy
timeFrame: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1
measure: Response rate to therapy (proportion of patients in the group showing a reduction in pain/discomfort in the upper abdomen on the VAS by more than 30%) by day 29 from the start of therapy
timeFrame: Day 29 ± 1
measure: Response rate to therapy (proportion of patients in the group showing a reduction in pain/discomfort in the upper abdomen on the VAS by 50% or more) by day 29 from the start of therapy
timeFrame: Day 29 ± 1
measure: Change in manifestations of dyspeptic disorders according to the GSRS questionnaire scores on days 8, 15, 22, and 29 from the start of treatment
timeFrame: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1
measure: Change in quality of life based on the total score from the SF-36 questionnaire by day 29 from the start of therapy;
timeFrame: Day 29 ± 1
measure: Average reduction in pain/discomfort severity in the upper abdomen on the VAS by days 8, 15, and 22 from the start of treatment
timeFrame: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1
measure: Safety and Tolerability: adverse event (AE) rate
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 36 ± 2 for each participant
measure: Safety and Tolerability: adverse event (AE) number
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 36 ± 2 for each participant
measure: Safety and Tolerability: AEs associated with the study drug
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 36 ± 2 for each participant
measure: Safety and Tolerability: SAEs associated with the study drug
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 36 ± 2 for each participant
measure: Safety and Tolerability: treatment discontinuation
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 36 ± 2 for each participant
measure: Safety and Tolerability: vital signs - systolic blood pressure (SBP)
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: vital signs - diastolic blood pressure (DBP)
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: vital signs - respiratory rate (RR)
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: vital signs - heart rate (HR)
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: vital signs - body temperature
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: cardiovascular system
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: respiratory system
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: digestive tract
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: endocrine system
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: musculoskeletal system
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: nervous system
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: sensory systems
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Physical examination results: skin/visible mucous membranes
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - hemoglobin
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - hematocrit
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - red blood cell count
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - platelet count
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - leukocyte count
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - erythrocyte sedimentation rate
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - myelocytes
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - band neutrophils
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - segmented neutrophils
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - eosinophils
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - basophils
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - monocytes
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: clinical blood test - lymphocytes
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - glucose
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - cholesterol
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - protein
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - bilirubin
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - creatinine
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - alkaline phosphatase
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - alanine transaminase
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - aspartate transaminase
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: blood chemistry - gamma-GTP
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: urinalysis - specific gravity
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: urinalysis - pH
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: urinalysis - protein
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: urinalysis - glucose
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: urinalysis - red blood cells
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Results of laboratory and instrumental examinations: urinalysis - white blood cells
timeFrame: Screening, day 15 ± 1, day 29 ± 1
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval
timeFrame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1
Other outcomes:
Locations:
city: Engels
country: Russian Federation
facility: State autonomous health care institution "Engels City Clinical Hospital No. 1"
city: Ivanovo
country: Russian Federation
facility: Ivanovo Kuvaev Clinical Hospital
city: Moscow
country: Russian Federation
facility: State Budgetary Institution of Healthcare of Moscow "City Polyclinic No. 2 of the Moscow Department of Healthcare"
city: Moscow
country: Russian Federation
facility: Unimed-C Jsc
city: Moscow
country: Russian Federation
facility: The State Budgetary Healthcare Institution of the Moscow Region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "ErSi Medical"
city: Perm
country: Russian Federation
facility: Professors' Clinic LLC.
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Energy of Health"
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Healthcare Institution "City Polyclinic No. 117"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Clinic Zvezdnaya"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Meili"
city: Saint Petersburg
country: Russian Federation
facility: State Budgetary Institution "St. Petersburg Research Institute of Emergency Care named after I.I. Djanelidze"
city: Samara
country: Russian Federation
facility: Private institution of higher education "Medical University 'Reavis'"
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "Medical Center Eco-Safety"
city: Tol'yatti
country: Russian Federation
facility: Association "Regional Medical Center 'Open Medicine'"
city: Veliky Novgorod
country: Russian Federation
facility: LLC "Polyclinic Polimedika Veliky Novgorod"
city: Yaroslavl
country: Russian Federation
facility: Limited Liability Company "Medical Center for Diagnosis and Prevention Plus"
Study officials:
References: