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

Официальное название

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

Обзор

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

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1]
• Safety and Tolerability: adverse event (AE) rate [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Россия · 17 центров

• 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
• … и ещё 9 центров

Идентификаторы

NCT: NCT06842966 · GIB-02-03-2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗