Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Abbott
• Collaborators: Ascent; Catalent; ClinIntel; Datamap

Criteria

Inclusion criteria:

• Signed informed consent given by the subject

• Age ≥ 18 years to 75 years

• Chronic liver disease due to alcoholic liver disease

• Compensated alcoholic liver disease, defined as having a Maddrey Score < 32 and not being treated with pentoxifylline or prednisolone within 6 months prior to the study

• History of chronic alcohol use, defined as, history of consumption of > 40 g of alcohol per day for females and > 80 g alcohol per day for males for more than 5 years prior to enrolment

• Subjects who abstain from alcohol for more than 2 weeks and will not consume alcohol during the study

• Subjects with Intrahepatic Cholestasis (IHC):

• ALP: more than 1.5 x upper normal limit and

• γGT: more than 3 x upper normal limit

• Subjects with additional serum conjugated bilirubin (SCB) > Upper Limit of Normal (ULN) will be selected for initial IV treatment

Exclusion Criteria:

• 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