Health Condition 1: K703- Alcoholic cirrhosis of liver Health Condition 2: K700- Alcoholic fatty liver Health Condition 3: K701- Alcoholic hepatitis
Conditions
Interventions
Intervention1: Heptral™ (Ademetionine tablets) manufactured by Akums Drugs and Pharmaceutical Limited and marketed by Abbott India Limited.: Each enteric coated tablet is of 400 mg and contains: Ademe
Sponsors
Abbott India Limited
AKUMS DRUGS AND PHARMACEUTICALS LIMITED
Eligibility
Inclusion criteria
Inclusion criteria: 1 Male or female adult patients aged 18 years to 65 years. 2 Patient history that reliably indicates alcohol abuse (Heavy alcohol consumption [defined as greater than 40 grams per day on average in women and greater than 60 grams per day on average in men for a minimum of 6 months and within the 6 weeks prior to study enrollment]. 3 Ultrasound evidence of liver disease changes along with elevated hepatic transaminases (ALT greater than or equal to 2 times ULN) at screening visit (visit 1). 4 Patients diagnosed with ALD inclusive of FL, AH, and AC as per physicians’ discretion based on the following: Fatty Liver: The presumptive diagnosis of FL will be made as per treating physician’s discretion based on the history of heavy alcohol use, ultrasound changes and elevated liver enzymes Alcoholic Hepatitis: Patients with Maddrey discriminant function LESS THAN 32 calculated as 4.6 × patient’s PT–control PT (seconds) + serum bilirubin (mg/dL) will be included in the study. The presumptive diagnosis for AH will be as per physician’s discretion, based on a history of heavy alcohol use, jaundice, and the absence of other possible causes of hepatitis. The combination of an elevated AST level (less than 300 IU/mL) and a ratio of the AST/ALT > 2 X ULN, a total serum bilirubin level of greater than 5 mg/dL (86 µmol/L), an elevated international normalized ratio (INR), and neutrophilia in a patient with a history of heavy alcohol use will be correlated for diagnosis of AH Alcoholic Cirrhosis (AC): The presumptive diagnosis of AC will be based on treating physician’s discretion in patients who are diagnosed with AC as per earlier biopsy report (not more than 6 months old) or liver stiffness measurement (FibroScan) & co-relating with the present ultrasound findings. 5 Treatment naïve patients (not have received any hepatoprotective agents for the existing disease within the last 6 months) 6 Patients who agree to abstain from alcohol consumption for 120 days (4 months) of study duration. 7 Patients willing to participate in the study, sign the informed consent form and ready to comply with protocol requirements
Exclusion criteria
Exclusion criteria: 1 Patients with a history of consumption of steatogenic medications in the 6 months prior to screening, such as amiodarone, methotrexate, tamoxifen, valproate, anti-retroviral medicine, NSAIDs, statins, neuroleptics, anti-convulsants, corticosteroids, etc as per available records. 2 Patients with other causes of chronic liver disease (NAFLD, autoimmune liver diseases, viral hepatitis (Hepatitis B virus and Hepatitis C virus), Wilson’s disease, hemochromatosis) and metabolic syndrome. 3 Patients with severe liver disease such as with Child-Pugh Class B or C and with any end-stage liver disease 4 Patients with severe cardiac and renal disease (serum creatinine greater than or equal to 2.0 mg/dL) 5 Hepatocellular carcinoma 6 History of malignancy or active neoplasm 7 Contraindications to Heptral™ (Ademetionine tablets) treatment, including hypersensitivity to active substance or any ingredient 8 Patients 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) 9 Women of childbearing potential with a positive urine pregnancy test during screening or unwillingness to use an effective form of birth control during the study 10 Lactating women 11 Patients after liver transplantation 12 History of major depression or bipolar disease 13 Any condition that in the opinion of the investigator does not justify the patient’s inclusion in the study 14 Patient on any treatment with other drugs claimed for treatment of ALD (pentoxyphylline, steroids, ursodeoxycholic acid, acetyl cholinesterase enzyme inhibitors antioxidants such as vitamin E, vitamin C, GSH, alpha-tocopherol, or non-prescribed complementary alternative medications [including dietary supplements,] or any medicine in clinical trials for ALD 15 Clinical or laboratory evidence of hepatic decompensation as defined by the presence of the following abnormalities: a) History of ascites, hepatic encephalopathy, varices or bleeding b) Patients with severe AH (Maddrey discriminant function greater than 32 calculated as 4.6×patient’s prothrombin time–control prothrombin time (seconds) + serum bilirubin (mg/dL)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the effectiveness of Heptral™ (Ademetionine tablets) on change in serum alanine aminotransferase (ALT) at 120 days (4 months) of treatment as compared to baseline in patients with alcoholic liver disease (ALD) inclusive of fatty liver (FL), alcoholic hepatitis (AH), and alcoholic cirrhosis (AC)Timepoint: At 120 days (4 months) of treatment as compared to baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the tolerability and safety of Heptral™ (Ademetionine tablets) therapy during the trialTimepoint: Entire study duration;To evaluate the effectiveness of Heptral™ (Ademetionine tablets) on change in serum ALT at 30 days of treatment as compared to baseline in patients with ALD inclusive of FL, AH, and ACTimepoint: Day 30;To evaluate the effectiveness of Heptral™ (Ademetionine tablets) on change in serum AST/ALT ratio at 30 days and 120 days (4 months) of treatment as compared to baseline in patients with ALD inclusive of FL, AH, and ACTimepoint: Day 30 and Day 120;To evaluate the effectiveness of Heptral™ (Ademetionine tablets) on changes in health-economic burden (number of days of hospitalization, number of days off-work, and number of visits to healthcare services as an outpatient) at 30 days and 120 days (4 months) of treatment as compared to baseline in patients with ALD inclusive of FL, AH, and ACTimepoint: Day 30 and Day 120;To evaluate the effectiveness of Heptral™ (Ademetionine tablets) on changes in signs and symptoms of jaundice, fatigue, and pruritus as assessed by the investigator at 30 days and 120 days (4 months) of treatment as compared to baseline in patients with ALD inclusive of FL, AH, and ACTimepoint: Day 30 and Day 120 | — |
Countries
India
Contacts
Public ContactDr Shivani Acharya
Abbott India Limited
Outcome results
None listed