Clearance of NRL972 in Patients With Cirrhosis, Nonalcoholic Steatohepatitis (NASH) and in Healthy Volunteers

Inclusion criteria

General - all subjects

• Males or females (females of non-childbearing potential or of childbearing potential while taking medically appropriate contraception)
• Caucasian
• BMI: between 19 and 34 kg.m-2
• BW: between 45 and 110 kg
• willing and able to provide informed consent Healthy volunteers (group N)
• Age: 18 - 40 years (inclusive) e.g. > 60 years
• Assessed as healthy based on the pre study examination Hepatic cirrhosis
• Age: 18 - 75 years
• stable compensated liver cirrhosis (cryptogenic, posthepatic, alcoholic) with histo-logical or macroscopic (e.g. laparascopy, biopsy, ultrasound sonography or other adequate imaging techniques) confirmation Nonalcoholic steatohepatitis (NASH)
• Age: 18 - 75 years
• Diagnosis of NASH confirmed by liver biopsy

Exclusion criteria

General - all subjects

• Previous participation in the trial
• Participant in any other trial during the last 90 days
• Donation of blood during the last 60 days or a history of blood loss exceeding 450 mL within the last 3 months
• History of any clinically relevant allergy
• Uncontrolled diabetes mellitus or any further intolerability of the Galactose test
• Presence of acute or chronic infection
• Resting systolic blood pressure > 160 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg
• Clinically relevant ECG-abnormalities, prolonged QTc with > 450 msec in males and > 460 msec in females in particular
• Clinically relevant ECG-abnormalities that constitute a contraindication for the Lido-cain-MEG'-X-test
• Positive HIV test
• Positive alcohol or urine drug test on recruitment
• Daily use of > 30 gr alcohol
• Smoking more than 15 cigarettes/day or equivalent of other tobacco products
• Use of prohibited medication
• Suspicion or evidence that the subject is not trustworthy and reliable
• Suspicion or evidence that the subject is not able to make a free consent or to under-stand the information in this regard

General - all females

• Positive pregnancy test
• Lactating
• Not using appropriate contraception in premenopausal women All healthy subjects
• Presence or history of any relevant comorbidity (list of past and present diseases will be reviewed by an expert panel)
• Presence of any relevant abnormality in the laboratory safety tests, especially low haemoglobin, increased liver enzymes, reduced serum creatinine (laboratory test abnormalities will be reviewed by an expert panel)
• Positive serology for HBsAg, anti HBc and anti HCV
• History of alcohol and/or drug abuse.

Patients with hepatic disease

• Biliary liver cirrhosis
• Liver impairment due to space-occupying processes (e.g. carcinoma)
• State after liver transplantation or patient scheduled for liver transplantation
• Fluctuating or rapidly deteriorating hepatic function
• Significant bleeding diathesis
• Oesophageal bleeding within the last 8 weeks before study entry
• Ascites > 6 L on abdominal US
• Number Connection test: time to connect 25 consecutive numbers > 30 sec
• Presence or history of any relevant comorbidity other than hepatic disease (list of past and present diseases will be reviewed by an expert panel)
• Clinically relevant abnormal laboratory values other than those associated or sufficiently explained by the existing liver disease (laboratory test abnormalities will be reviewed by an expert panel)
• History of drug or alcohol abuse within 2 months prior to dosing