Comparative Study of REMAXA®, Enteric-coated Tablets and REMAXOL®, Solution for Infusions, in Intrahepatic Cholestasis

Multicenter Comparative Randomized Study to Assess Safety and Efficacy and Select the Optimal Dosage Regimen of REMAXA®, Enteric-coated Tablets, in Comparison With REMAXOL®, Solution for Infusions, in Patients With Intrahepatic Cholestasis Caused by Chronic Diffuse Liver Diseases

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.

Study Overview

• Status: Completed
• Conditions: Cholestasis, Intrahepatic
• Intervention / Treatment: Drug: Remaxa, enteric-coated tablets; Drug: Remaxol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 328
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 196143
    • Research Center for Eco-safety, Ltd.
  • Saint-Petersburg, Russian Federation, 197706
    • City Hospital of the Holy Martyr Elizabeth
  • Samara, Russian Federation, 443063
    • Medical Company "Hepatologist" Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I-1; Intake of REMAXA, enteric-coated tablets, 2 tablets 3 times a day for 10 days	Drug: Remaxa, enteric-coated tablets; enteric-coated tablets; Other Names: inosine, methionine, nicotinamide, succinic acid
Experimental: Group I-2; Intake of REMAXA, enteric-coated tablets, 2 tablets 2 times a day for 10 days	Drug: Remaxa, enteric-coated tablets; enteric-coated tablets; Other Names: inosine, methionine, nicotinamide, succinic acid
Experimental: Group I-3; Intake of REMAXA, enteric-coated tablets, 2 tablets once a day for 10 days	Drug: Remaxa, enteric-coated tablets; enteric-coated tablets; Other Names: inosine, methionine, nicotinamide, succinic acid
Active Comparator: Group I-4; Infusions of REMAXOL, solution for infusion, by intravenous drip, 400 ml once a day for 10 days.	Drug: Remaxol; solution for infusions; Other Names: inosine + meglumine + methionine + nicotinamide + succinic acid
Experimental: Group II-1; Intake of REMAXA, enteric-coated tablets, during 10 days according to optimal dosing regimen established during stage I.	Drug: Remaxa, enteric-coated tablets; enteric-coated tablets; Other Names: inosine, methionine, nicotinamide, succinic acid
Active Comparator: Group II-2; Infusions of REMAXOL, solution for infusion, by intravenous drip, 400 ml once a day for 10 days.	Drug: Remaxol; solution for infusions; Other Names: inosine + meglumine + methionine + nicotinamide + succinic acid
Placebo Comparator: Group II-3; Intake of Placebo, enteric-coated tablets, during 10 days, analogous to dosing regimen in Group II-1	Drug: Placebo; enteric-coated tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of responders to treatment in the study groups	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.	11 days

Collaborators and Investigators

• Sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
• Investigators: Study Director: Tatiana V Kharitonova, MD PhD, STPF POLYSAN

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2023
• Primary Completion (Actual): September 24, 2024
• Study Completion (Actual): October 10, 2024

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: intrahepatic cholestasis; chronic diffuse liver disease; Biliary Stasis, Intrahepatic
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Cholestasis; Cholestasis, Intrahepatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Micronutrients; Vitamin B Complex; Vitamins; Vasodilator Agents; Hypolipidemic Agents; Lipid Regulating Agents; Niacin; Niacinamide; Nicotinic Acids
• Other Study ID Numbers: RXA-II-III-Chol-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No