Biliary Dyskinesia, Chronic Cholecystitis
Conditions
Brief summary
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
DRUG4-MUST
128 mg of trimebutine 4-methylumbelliferyl sulfate tablet.
DRUGPlacebo
Placebo tablet.
Sponsors
Valenta Pharm JSC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females 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 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). 7. Signed and dated informed consent from. 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 past diagnoses). 10. History of gastrointestinal surgical procedures, including but not limited to endoscopic papillotomy and cholecystectomy, exept for appendectomy. 11. Use of prohibited therapy medications within 3 days prior to randomization. 12. History of mental illnesses. 13. 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. HIV, syphilis, viral hepatitis B or C, including in history. 17. Lactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome. 18. Liver cirrhosis. 19. Hypersensitivity to the active ingridient or any of the excipients 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. History of surgery within 6 month prior to screening. 29. Women during pregnancy or lactation; women planning to become pregnant 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 investigator's judgement, may preclude the patient's participation in the study.
Exclusion criteria
1. Incorrect enrollment of a patient in the study (failure to meet inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average reduction in the severity of pain/discomfort in the upper abdomen on the VAS by day 29 compared to baseline | Day 29 ± 1 | Visual analogue scale (VAS) from 0 to 100 mm, where 0 is no pain, and 100 is the worst pain one can imagine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 29 ± 1 | Visual analogue scale (VAS) from 0 to 100 mm, where 0 is no pain, and 100 is the worst pain one can imagine |
| 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 | Day 29 ± 1 | Visual analogue scale (VAS) from 0 to 100 mm, where 0 is no pain, and 100 is the worst pain one can imagine |
| Change in manifestations of dyspeptic disorders according to the GSRS questionnaire scores on days 8, 15, 22, and 29 compared to baseline | Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1 | The Gastrointestinal Symptom Rating Scale (GSRS) is a self-administered questionnaire designed to assess gastrointestinal symptoms and their severity. It consists of 15 items categorized into five domains: Abdominal pain (including stomach pain and nausea), Reflux (heartburn and acid reflux), Indigestion (bloating, burping, and flatulence), Constipation (hard stools and incomplete evacuation), Diarrhea (loose stools and urgency). Respondents rate their symptoms on a 7-point Likert scale, where 1 indicates no discomfort and 7 indicates very severe discomfort. |
| Change in quality of life based on the total score from the SF-36 questionnaire by day 29 compared to baseline | Day 29 ± 1 | SF-36 (Short Form 36 Health Survey) is a self-reported questionnaire. It consists of 36 items that cover eight health domains: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Bodily pain, General health perceptions, Vitality (energy and fatigue), Social functioning, Mental health. SF-36 produces a profile of scores for each domain, which can be summarized into two main components: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Scores range from 0 to 100, where lower scores indicate greater disability and higher scores indicate better health. |
| Average reduction in pain/discomfort severity in the upper abdomen on the VAS by days 8, 15, and 22 compared to baseline | Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1 | Visual analogue scale (VAS) from 0 to 100 mm, where 0 is no pain, and 100 is the worst pain one can imagine |
| Safety and Tolerability: adverse event (AE) rate | 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 | Frequency of adverse events (AEs) or serious AEs (SAEs) |
| Safety and Tolerability: adverse event (AE) number | 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 | Number of adverse events (AEs) or serious AEs (SAEs) |
| Safety and Tolerability: AEs associated with the study drug | 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 | Number and frequency of AEs associated with the study drug |
| Safety and Tolerability: SAEs associated with the study drug | 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 | Number and frequency of SAEs associated with the study drug |
| Safety and Tolerability: treatment discontinuation | 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 | Percentage of patients who discontinued treatment due to the occurrence of AEs/SAEs |
| Safety and Tolerability: vital signs - systolic blood pressure (SBP) | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | SBP, mmHg |
| Safety and Tolerability: vital signs - diastolic blood pressure (DBP) | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | DBP, mmHg |
| Safety and Tolerability: vital signs - respiratory rate (RR) | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | RR, breaths per minute |
| Safety and Tolerability: vital signs - heart rate (HR) | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | HR, beats per minute |
| Safety and Tolerability: vital signs - body temperature | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | Body temperature, Celsius scale |
| Physical examination results: cardiovascular system | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the cardiovascular system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results: respiratory system | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the respiratory system on physical examination (normal condition or list of abnormal conditions, if any)(normal condition or list of abnormal conditions, if any) |
| Physical examination results: digestive tract | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the digestive tract on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results: endocrine system | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the endocrine system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results: musculoskeletal system | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the musculoskeletal system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results: nervous system | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the nervous system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results: sensory systems | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the sensory systems on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results: skin/visible mucous membranes | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | An assessment of the condition of the skin/visible mucous membranes on physical examination (normal condition or list of abnormal conditions, if any) |
| Results of laboratory and instrumental examinations: clinical blood test - hemoglobin | Screening, day 15 ± 1, day 29 ± 1 | Hemoglobin (g/L) |
| Results of laboratory and instrumental examinations: clinical blood test - hematocrit | Screening, day 15 ± 1, day 29 ± 1 | Hematocrit (%) |
| Results of laboratory and instrumental examinations: clinical blood test - red blood cell count | Screening, day 15 ± 1, day 29 ± 1 | Red blood cell count (cells/L) |
| Results of laboratory and instrumental examinations: clinical blood test - platelet count | Screening, day 15 ± 1, day 29 ± 1 | Platelet count (cells/L) |
| Results of laboratory and instrumental examinations: clinical blood test - leukocyte count | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte count (cells/L) |
| Results of laboratory and instrumental examinations: clinical blood test - erythrocyte sedimentation rate | Screening, day 15 ± 1, day 29 ± 1 | Erythrocyte sedimentation rate (mm/h) |
| Results of laboratory and instrumental examinations: clinical blood test - myelocytes | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (myelocytes, %) |
| Results of laboratory and instrumental examinations: clinical blood test - band neutrophils | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (band neutrophils, %) |
| Results of laboratory and instrumental examinations: clinical blood test - segmented neutrophils | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (segmented neutrophils, %) |
| Results of laboratory and instrumental examinations: clinical blood test - eosinophils | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (eosinophils, %) |
| Results of laboratory and instrumental examinations: clinical blood test - basophils | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (basophils, %) |
| Results of laboratory and instrumental examinations: clinical blood test - monocytes | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (monocytes, %) |
| Results of laboratory and instrumental examinations: clinical blood test - lymphocytes | Screening, day 15 ± 1, day 29 ± 1 | Leukocyte formula (lymphocytes, %) |
| Results of laboratory and instrumental examinations: blood chemistry - glucose | Screening, day 15 ± 1, day 29 ± 1 | Glucose concentration (mmol/L) |
| Results of laboratory and instrumental examinations: blood chemistry - cholesterol | Screening, day 15 ± 1, day 29 ± 1 | Total cholesterol concentration (mmol/L) |
| Results of laboratory and instrumental examinations: blood chemistry - protein | Screening, day 15 ± 1, day 29 ± 1 | Total protein concentration (g/L) |
| Results of laboratory and instrumental examinations: blood chemistry - bilirubin | Screening, day 15 ± 1, day 29 ± 1 | Total bilirubin concentration (micromol/L) |
| Results of laboratory and instrumental examinations: blood chemistry - creatinine | Screening, day 15 ± 1, day 29 ± 1 | Creatinine concentration (micromol/L) |
| Results of laboratory and instrumental examinations: blood chemistry - alkaline phosphatase | Screening, day 15 ± 1, day 29 ± 1 | Alkaline phosphatase activity (U/L) |
| Results of laboratory and instrumental examinations: blood chemistry - alanine transaminase | Screening, day 15 ± 1, day 29 ± 1 | Alanine transaminase activity (U/L) |
| Results of laboratory and instrumental examinations: blood chemistry - aspartate transaminase | Screening, day 15 ± 1, day 29 ± 1 | Aspartate transaminase activity (U/L) |
| Results of laboratory and instrumental examinations: blood chemistry - gamma-GTP | Screening, day 15 ± 1, day 29 ± 1 | Gamma-glutaryl transpeptidase activity (U/L) |
| Results of laboratory and instrumental examinations: urinalysis - specific gravity | Screening, day 15 ± 1, day 29 ± 1 | Specific gravity of the urine |
| Results of laboratory and instrumental examinations: urinalysis - pH | Screening, day 15 ± 1, day 29 ± 1 | pH of the urine |
| Results of laboratory and instrumental examinations: urinalysis - protein | Screening, day 15 ± 1, day 29 ± 1 | Protein concentration (g/L) |
| Change in the total score of gastrointestinal symptom severity according to the GSRS questionnaire on days 8, 15, 22, and 29 compared to baseline | Day 8 ± 1, 15 ± 1, 22 ± 1, and 29 ± 1 | The Gastrointestinal Symptom Rating Scale (GSRS) is a self-administered questionnaire designed to assess gastrointestinal symptoms and their severity. It consists of 15 items categorized into five domains: Abdominal pain (including stomach pain and nausea), Reflux (heartburn and acid reflux), Indigestion (bloating, burping, and flatulence), Constipation (hard stools and incomplete evacuation), Diarrhea (loose stools and urgency). Respondents rate their symptoms on a 7-point Likert scale, where 1 indicates no discomfort and 7 indicates very severe discomfort. |
| Results of laboratory and instrumental examinations: urinalysis - red blood cells | Screening, day 15 ± 1, day 29 ± 1 | Red blood cell content (number in sight) |
| Results of laboratory and instrumental examinations: urinalysis - white blood cells | Screening, day 15 ± 1, day 29 ± 1 | White blood cell content (number in sight) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: heart rate (beats per minute) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: PQ interval (is the period, measured in milliseconds, that extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: QRS complex (the QRS complex is the combination of three of the graphical deflections seen on a typical electrocardiogram) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval | Screening, day 1, day 8 ± 1, day 15 ± 1, day 22 ± 1, day 29 ± 1 | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: corrected QT interval (distance from the beginning of the QRS complex to the end of the T wave) (Frederica correction) |
| Results of laboratory and instrumental examinations: urinalysis - glucose | Screening, day 15 ± 1, day 29 ± 1 | Glucose concentration (mmol/L) |
Countries
Russia
Outcome results
None listed