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

NCT06183242 | Completed Phase 2

• 1 other identifier: RXA-II-III-Chol-2022
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 3

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.

Conditions

Cholestasis, Intrahepatic

Keywords

intrahepatic cholestasis; chronic diffuse liver disease; Biliary Stasis, Intrahepatic

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (7)

Group I-1

EXPERIMENTAL

Intake of REMAXA, enteric-coated tablets, 2 tablets 3 times a day for 10 days

Drug: Remaxa, enteric-coated tablets

Group I-2

EXPERIMENTAL

Intake of REMAXA, enteric-coated tablets, 2 tablets 2 times a day for 10 days

Drug: Remaxa, enteric-coated tablets

Group I-3

EXPERIMENTAL

Intake of REMAXA, enteric-coated tablets, 2 tablets once a day for 10 days

Drug: Remaxa, enteric-coated tablets

Group I-4

ACTIVE COMPARATOR

Infusions of REMAXOL, solution for infusion, by intravenous drip, 400 ml once a day for 10 days.

Drug: Remaxol

Group II-1

EXPERIMENTAL

Intake of REMAXA, enteric-coated tablets, during 10 days according to optimal dosing regimen established during stage I.

Drug: Remaxa, enteric-coated tablets

Group II-2

ACTIVE COMPARATOR

Infusions of REMAXOL, solution for infusion, by intravenous drip, 400 ml once a day for 10 days.

Drug: Remaxol

Group II-3

PLACEBO COMPARATOR

Intake of Placebo, enteric-coated tablets, during 10 days, analogous to dosing regimen in Group II-1

Drug: Placebo

Interventions

Remaxa, enteric-coated tablets DRUG

enteric-coated tablets

Also known as: inosine, methionine, nicotinamide, succinic acid

Group I-1; Group I-2; Group I-3; Group II-1

Remaxol DRUG

solution for infusions

Also known as: inosine + meglumine + methionine + nicotinamide + succinic acid

Group I-4; Group II-2

Placebo DRUG

enteric-coated tablets

Group II-3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18 to 70 years (inclusive).
• 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).
• 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.
• Negative pregnancy test in female patients.
• Consent to the use of adequate contraceptive methods or complete abstinence from sexual activity for the study period.
• 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.
• Signed informed consent.

You may not qualify if:

• Cirrhotic stage of chronic liver disease (Class A-C by Child-Pugh).
• Hyperbilirubinemia more than 100 µmol/l.
• GGTP level is more than 10 upper normal limits.
• History of autoimmune liver disease.
• Acute viral hepatitis (B, C, D).
• Any somatic diseases in the stage of decompensation.
• Hypersensitivity and/or intolerance to any component of the study drug /comparator drug.
• Pregnancy or lactation period.
• Peptic ulcer of the stomach and/or duodenum, and/or erosive gastritis in the acute phase.
• History of chronic kidney disease C4-C5 and/or known glomerular filtration rate \<30 ml/min.
• Regular intake of more than 2 units. alcohol per week.
• Unstable angina.
• Chronic heart failure of III-IV functional class by New York Heart Association (NYHA) classification.
• History of cancer within the last 5 years, mental illness, HIV infection, tuberculosis, drug addiction.
• Mental, physical and other reasons that prevent the patient adequately behave and correctly fulfill the conditions of the study protocol.

Sponsors & Collaborators

• POLYSAN Scientific & Technological Pharmaceutical Company: lead

Study Sites (3)

Research Center for Eco-safety, Ltd.

Saint Petersburg, 196143, Russia

Location

City Hospital of the Holy Martyr Elizabeth

Saint Petersburg, 197706, Russia

Location

Medical Company "Hepatologist" Ltd.

Samara, 443063, Russia

Location

MeSH Terms

Conditions

Cholestasis, Intrahepatic

Interventions

Inosine; Methionine; Niacinamide; Succinic Acid; Remaxol; Meglumine

Condition Hierarchy (Ancestors)

Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids, Essential; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Neutral; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Sorbitol; Sugar Alcohols; Alcohols; Hexosamines; Amino Sugars; Carbohydrates

Study Officials

• Tatiana V Kharitonova, MD PhD

  STPF POLYSAN

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter prospective two-stage comparative randomized parallel group study with placebo control

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: December 27, 2023
• Study Start: May 27, 2023
• Primary Completion: September 24, 2024
• Study Completion: October 10, 2024
• Last Updated: April 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (3)