Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption
- Conditions
- Intrahepatic Cholestasis Associated With Alcoholic Liver Disease
- Interventions
- Registration Number
- NCT02200029
- Lead Sponsor
- Abbott
- Brief Summary
A research study of an approved drug called Heptral®, ademetionine, to treat adults with intrahepatic cholestasis (a condition where bile cannot flow from the liver to the duodenum) in pre-cirrhotic and cirrhotic states. Experience from clinical studies in subjects with liver disease has shown that ademetionine is effective.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
Not provided
- Subjects with a known hypersensitivity to the active substance of ademetionine or to any of the inactive ingredients
- Subjects with extrahepatic cause of cholestasis (proven by ultrasound or described in medical history)
- Diagnosis of human immunodeficiency virus (HIV) in medical history
- Subjects with chronic liver disease Child-Pugh class C
- Subjects in the decompensation stage of ALD (such as Maddrey Score >32)
- Subjects with primary sclerosing cholangitis (PSC)
- Subjects with primary biliary cirrhosis (PBC)
- Any form of malignancy within the past 5 years and/or basal cell carcinoma and squamous cell carcinoma of the skin within the past two years
- Subjects with drug-induced liver disease
- History of active substance abuse (oral, inhaled or injected) within one year prior to the study
- Subjects with renal impairment (creatinine level of >2.0 mg/dL or > 150 µmol/l)
- Subjects with known genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase deficiency, Vitamin B12 metabolism defect) or known folate, Vitamin B6 or B12 deficiency
- Subjects on total parenteral nutrition in the year prior to screening
- Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery)
- Subjects after liver transplantation and subjects on the waiting list for liver transplantation
- Subjects with any of the following disease in medical history:
- Viral hepatitis (serum positive HBcAb or Hepatitis C Virus (HCV) RNA)
- Evidence of autoimmune liver disease
- Wilson´s disease
- Hemochromatosis
- Alpha-1-antitrypsin deficiency
- Subjects with history of biliary diversion
- History of major depression or bipolar disease
- Women of childbearing potential: positive urine pregnancy test during screening or unwillingness to use an effective form of birth control during the study.
- Breastfeeding women
- Any condition that, in the opinion of the investigator, does not justify the patient's inclusion into the study
- Investigational drug intake within one month prior to the study
- Active, serious medical disease other than ALD with likely life-expectancy less than five years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ademetionine oral Ademetionine tablet - Ademetionine IV Ademetionine IV+tablet -
- Primary Outcome Measures
Name Time Method Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT) from baseline up to the end of treatment visit (56-60 days) Improvement of ALP or γGT after 8 weeks of treatment with ademetionine compared to baseline
- Secondary Outcome Measures
Name Time Method The intensity of clinical symptoms (jaundice, pruritus, fatigue and depressed mood) will be recorded for each symptom separately using six categories: No symptoms (0), minimum (1) to maximum (5). At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment Record of intensity of jaundice, pruritus, fatigue and depressed mood compared to baseline
Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter) At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment Improvement of ALP, γGT and serum total and conjugated bilirubin, ALT and AST compared to baseline
Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment \>20% reduction of ALP or γGT or normalization of ALP or γGT compared to baseline
Trial Locations
- Locations (12)
Research facility ORG-000961
🇷🇺Moscow, Russian Federation
Research facility ORG-000967
🇷🇺St. Petersburg, Russian Federation
Research facility ORG-000966
🇷🇺St. Petersburg, Russian Federation
Research facility ORG-000968
🇷🇺St. Petersburg, Russian Federation
Research facility ORG-000965
🇷🇺St. Petersburg, Russian Federation
Research facility ORG-000969
🇷🇺Yaroslavl, Russian Federation
Research facility ORG-000962
🇷🇺Moscow, Russian Federation
Research facility ORG-000957
🇷🇺Moscow, Russian Federation
Research facility ID ORG-000960
🇷🇺Moscow, Russian Federation
Research facility ID ORG-000726
🇷🇺Moscow, Russian Federation
Research facility ORG-000970
🇷🇺St. Petersburg, Russian Federation
Research facility ORG-000958
🇷🇺Troitsk, Russian Federation