Clearance of NRL972 in Patients With Cirrhosis and in Healthy Volunteers

Inclusion criteria

Subjects meeting the following conditions will be eligible for enrolment:

General - all subjects

• Males or females (females of non-child-bearing potential or of child-bearing 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) and > 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

Exclusion criteria

Subjects of any of the following categories will be excluded from enrolment:

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 300 mL within the last 3 months
• History of any clinically relevant allergy
• Presence of acute or chronic infection
• Uncontrolled diabetes mellitus
• 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
• 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
• Presence of any relevant abnormality in the laboratory safety tests, especially low Hemoglobin, increased liver enzymes, reduced serum creatinine
• 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