Study to Investigate the Effects of Different Doses of S-adenosyl-L-methionine (SAMe) in Subjects With Nonalcoholic Fatty Liver Disease and Non-treated Matched Healthy Volunteers as Control Group

• Status: Completed
• Trial end date: 2014-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Investigation the Effects of Different Doses of SAMe in Subjects with Nonalcoholic Fatty Liver Disease and non-treated matched healthy volunteers as control group

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Abbott
• Collaborator: PPD

Criteria

Inclusion Criteria

• Subjects with non-alcoholic steatohepatitis based on histology in medical history within the last 3 years

• Subjects in a stable metabolic condition since histology for NASH (Non-alcoholic Steatohepatitis)

Exclusion Criteria

• Subjects with extrahepatic biliary obstruction

• 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

• 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)

• Subjects with a known hypersensitivity to the active substance (ademetionine) or methionine or to any of the inactive ingredients

• 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)

• 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)

• Extrahepatic cholestasis (proven by ultrasound)

• Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 upper limit of normal (ULN)

• Subject with serum total bilirubin (STB) > 5 ULN

• 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 (hepatitis B core antibody) or Hepatitis C Virus (HCV) ribonucleic acid (RNA)

• Evidence of autoimmune liver disease

• Wilson's disease

• Hemochromatosis

• Alpha-1-antitrypsin deficiency

• Known positivity for antibody to human immunodeficiency virus (HIV)

• Known heart failure of New York heart Association class 3 or 4

• Current or history of significant alcohol consumption for a period of more than three consecutive months within five years prior to screening (significant alcohol consumption is defined as > 3 U (unit)/day for men and > 2 U/day for women, on average) or binge drinking or inability to reliably quantify alcohol consumption.

• Clinical or histological evidence of cirrhosis F4

• Subjects with history of biliary diversion

• Subjects with uncontrolled diabetes mellitus defined by HbA1c (hemoglobin A1c) > 8.0 % at screening

• Concomitant medication of B12, folate, betaine or choline

• Concomitant treatment with glitazone within the past year prior to the study

• Subjects with known folate or B12 deficiency

• BMI (body mass index) > 40 kg/m2

• History of major depression diagnostic and statistical manual of mental disorders (DSM-IV) 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 with likely life-expectancy less than five years

• Uncooperative attitude or reasonable likelihood for non-compliance with the protocol or any other reason that, in the investigator's opinion, prohibits the inclusion of the subject into the study

• Legal incapacity or limited legal capacity, or who are incarcerated.

• Inability to return for scheduled visits.

• Inability to understand and follow the requirements of the protocol in the local language