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

Abbott

Status and phase

Completed

Phase 3

Conditions

Intrahepatic Cholestasis Associated With Alcoholic Liver Disease

Treatments

Drug: Ademetionine IV+tablet

Drug: Ademetionine tablet

Study type

Interventional

Funder types

Industry

Other

Identifiers

NCT02200029

M14-168

Details and patient eligibility

About

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.

Enrollment

75 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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