Cholestasis, Intrahepatic
Conditions
Keywords
intrahepatic cholestasis, chronic diffuse liver disease, Biliary Stasis, Intrahepatic
Brief summary
Chronic diffuse liver disease implies liver damage of various origin - viral hepatitis, the effect of xenobiotics (alcohol, drugs, medications, industrial toxins), metabolic disorders, non-alcoholic fatty liver disease. Intrahepatic cholestasis syndrome, or bile retention, occurs in 11-55% of cases of diffuse chronic liver diseases, usually leads to a worsening of the liver disease, a decrease in the effectiveness of treatment. The drug REMAXOL® is a solution for infusion, which has shown high effectiveness in the syndrome of intrahepatic cholestasis in cases of liver dysfunction due to acute or chronic damage. The study drug REMAXA® enteric-coated tablets is a hybrid drug which contains the same active metabolites as REMAXOL, i.e. inosine, methionine, nicotinamide, and succinic acid. The purpose of this study is to select the optimal dose and dosage regimen followed by evaluation safety and efficacy of REMAXA®, enteric-coated tablets, in comparison with REMAXOL®, solution for infusion, in patients who suffer from chronic diffuse liver diseases and have intrahepatic cholestasis.
Interventions
DRUGRemaxa, enteric-coated tablets
enteric-coated tablets
DRUGRemaxol
solution for infusions
DRUGPlacebo
enteric-coated tablets
Sponsors
POLYSAN Scientific & Technological Pharmaceutical Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
On stage 1, there will be no blinding (because REMAXOL is a solution for infusions). On stage 2, blinding will be ensured by placebo masking and drug assignment via IWRS.
Intervention model description
Multicenter prospective two-stage comparative randomized parallel group study with placebo control
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women aged 18 to 70 years (inclusive). 2. Patients with intrahepatic cholestasis syndrome in chronic diffuse liver diseases (alcoholic liver disease, toxic damage liver, liver fibrosis and sclerosis, fatty liver degeneration, chronic hepatitis) and/or with other liver dysfunction due to acute or chronic damage (toxic, alcoholic, viral, drug hepatitis). 3. Gamma-glutamyl transpeptidase (GGTP) exceeds the upper normal limit by 3 times or more and/or alkaline phosphatase (ALP) exceeds the upper normal limit by 1.5 times or more. 4. Negative pregnancy test in female patients. 5. Consent to the use of adequate contraceptive methods or complete abstinence from sexual activity for the study period. 6. Agreement to limit alcohol consumption to a maximum of 2 units alcohol per month (1 unit of alcohol is equivalent to 0.5 liters of beer, 200 ml of dry wine or 50 ml strong alcoholic drinks), or complete abstinence from drinking alcohol for period of the study. 7. Signed informed consent.
Exclusion criteria
1. Cirrhotic stage of chronic liver disease (Class A-C by Child-Pugh). 2. Hyperbilirubinemia more than 100 µmol/l. 3. GGTP level is more than 10 upper normal limits. 4. History of autoimmune liver disease. 5. Acute viral hepatitis (B, C, D). 6. Any somatic diseases in the stage of decompensation. 7. Regular use by the patient of medications prohibited in within the framework of this study, within 4 weeks before inclusion in the study and at throughout this study. 8. Hypersensitivity and/or intolerance to any component of the study drug /comparator drug. 9. Pregnancy or lactation period. 10. Peptic ulcer of the stomach and/or duodenum, and/or erosive gastritis in the acute phase. 11. History of chronic kidney disease C4-C5 and/or known glomerular filtration rate \<30 ml/min. 12. Regular intake of more than 2 units. alcohol per week. 13. Unstable angina. 14. Myocardial infarction 3 months or less before the expected date of inclusion. 15. Chronic heart failure of III-IV functional class by New York Heart Association (NYHA) classification. 16. History of cancer within the last 5 years, mental illness, HIV infection, tuberculosis, drug addiction. 17. Mental, physical and other reasons that prevent the patient adequately behave and correctly fulfill the conditions of the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of responders to treatment in the study groups | 11 days | The proportion of patients who responded to therapy, as indicated by any of the changes of laboratory parameters: a decrease in the level of gamma-glutamyltranspeptidase by at least 40% from the initial level and/or a decrease in the level of alkaline phosphatase by at least 30% from the initial level and/or a decrease in the level of total bilirubin not by less than 30% from the initial to the end of the therapeutic course in the REMAXA group compared to REMAXOL group. |
Countries
Russia
Outcome results
None listed