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 Administered at Various Doses in Patients With Chronic Cholecystitis and Biliary Dyskinesia

Overview

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

Interventions

• Drug 4-MUST
  128 mg of trimebutine 4-methylumbelliferyl sulfate tablet.
• Drug Placebo
  Placebo tablet.

Primary outcome measures

• Average reduction in the severity of pain/discomfort in the upper abdomen on the VAS by day 29 compared to baseline [Time frame: Day 29 ± 1]

Secondary outcome measures (12)

• Change in the total score of gastrointestinal symptom severity according to the GSRS questionnaire on days 8, 15, 22, and 29 compared to baseline [Time frame: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1]
• 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 compared to baseline [Time frame: Day 29 ± 1]
• 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 compared to baseline [Time frame: Day 29 ± 1]
• Change in manifestations of dyspeptic disorders according to the GSRS questionnaire scores on days 8, 15, 22, and 29 compared to baseline [Time frame: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1]
• Change in quality of life based on the total score from the SF-36 questionnaire by day 29 compared to baseline [Time frame: Day 29 ± 1]
• Average reduction in pain/discomfort severity in the upper abdomen on the VAS by days 8, 15, and 22 compared to baseline [Time frame: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1]
• Safety and Tolerability: adverse event (AE) rate [Time frame: 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]
• Safety and Tolerability: adverse event (AE) number [Time frame: 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]
• Safety and Tolerability: AEs associated with the study drug [Time frame: 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]
• Safety and Tolerability: SAEs associated with the study drug [Time frame: 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]
• Safety and Tolerability: treatment discontinuation [Time frame: 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]
• Safety and Tolerability: vital signs - systolic blood pressure (SBP) [Time frame: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1]

Eligibility criteria

Inclusion criteria

• Males and females aged 18-70 years.
• Presence of established gastrointestinal diseases: Chronic cholecystitis (K81.1); Dyskinesia of the bile duct or gallbladder (K82.8).
• 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.
• 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.
• 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.

Non-inclusion Criteria:

• Peptic ulcer disease, duodenal ulcer, erosive GERD.
• Toxic megacolon.
• Paralytic ileus.
• Gilbert's syndrome.
• Abdominal adhesion disease.
• Blood in stool, unexplained weight loss, fever, anemia.
• Inflammatory and erosive gastrointestinal diseases.
• Irritable bowel syndrome, non-specific ulcerative colitis, Crohn's disease.
• Oncological diseases of the gastrointestinal tract (including past diagnoses).
• History of gastrointestinal surgical procedures, including but not limited to endoscopic papillotomy and cholecystectomy, exept for appendectomy.
• 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).
• 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.
• 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 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).
• Diabetes mellitus in a state of subcompensation and decompensation.
• Systemic connective tissue diseases.
• Autoimmune diseases.
• Need for surgical and/or endovascular treatment and/or necessity for hemodialysis procedures.
• Epilepsy or seizures of unclear etiology, including in history.
• Alcoholism, substance abuse or drug addiction, including in history.
• Uncorrected electrolyte disturbances.
• 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.
• Lack of willingness to cooperate from the patient's side.
• Other conditions that, in the investigator's judgement, may preclude the patient's participation in the study.

Exclusion criteria

• Incorrect enrollment of a patient in the study (failure to meet inclusion/exclusion criteria at the time of randomization).
• 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.
• Patient non-compliance (a compliant patient is defined as one who has taken at least 202 and no more than 303 tablets).
• Requirement for prohibited concomitant therapy.
• If the investigator judges that comtinued participation in the study would harm the patient.
• Pregnancy or the need for breastfeeding in the patient.
• Gross violation by the patient of the study protocol procedures outlined in the patient information sheet (PIS).
• Withdrawal of informed consent (patient's unwillingness to continue participation in the study).
• 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).
• 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.
• Any other reasons, including administrative issues, that in the investigator's judgement may interfere with subject's ability to comlete the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Russia · 17 centers

• State autonomous health care institution "Engels City Clinical Hospital No. 1" — Engel's
• Ivanovo Kuvaev Clinical Hospital — Ivanovo
• State Budgetary Institution of Healthcare of Moscow "City Polyclinic No. 2 of the Moscow D — Moscow
• Unimed-C Jsc — Moscow
• The State Budgetary Healthcare Institution of the Moscow Region "Moscow Regional Research — Moscow
• Limited Liability Company "ErSi Medical" — Novosibirsk
• Professors' Clinic LLC. — Perm
• Limited Liability Company "Medical Center Eco-Safety" — Saint Petersburg
• … and 9 more centers

Identifiers

NCT: NCT06842966 · GIB-02-03-2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗