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

Overview

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.

Full Title of Study: “Open-Label Study With Ademetionine (Heptral®) in Subjects With Intrahepatic Cholestasis (IHC) Associated With Alcoholic Liver Disease (ALD)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 2015

Interventions

  • Drug: Ademetionine IV+tablet
    • IV ademetionine (500 mg/vial) for 2 weeks followed by oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 6 weeks
  • Drug: Ademetionine tablet
    • oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks

Arms, Groups and Cohorts

  • Experimental: Ademetionine IV
  • Experimental: Ademetionine oral

Clinical Trial Outcome Measures

Primary Measures

  • Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT)
    • Time Frame: 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 Measures

  • Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter)
    • Time Frame: 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
  • 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).
    • Time Frame: 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
  • Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations
    • Time Frame: 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Abbott
  • Collaborator
    • Ascent
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Suntje Sander-Struckmeier, PhD, Study Director, Abbott

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