Intervention: Bivalirudin
Trial phase: Phase 3
ATC code: B01AE06
SMILES: CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](N)Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 24
Group description: SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
Eligibility 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