multi-national cirrhosis study to characterise the association between the pharmacokinetics of nrl972 and disease severity.

Conditions: Hepatic Cirrhosis

Summary: this is a multi-centre, multi-national, open study to assess the pharmacokinetics of nrl972 in patients with hepatic cirrhosis ctp-classes a, b, and c (histologically confirmed by liver biopsy). the pharmacokinetics of nrl972 will be referenced to a clinical staging matrix obtained during a clinical work-up of patients with hepatic cirrhosis. patients to be studied will have histologically established hepatic cirrhosis or confirmed hepatic cirrhosis by an objective imaging study without confounding end-stage co-morbidity. within 14 days of confirming eligibility, the investigations will be conducted over 2-5 days with the test procedures (clinical laboratory tests, ultrasound (us)-investigations, gastroscopy, nrl972- and megx'-test). up to one week after the nrl972-test, a follow-up telephone call will be made.


Eligibility criteria:
inclusion criteria: subjects meeting the following conditions will be eligible for enrolment: * patient has given his or her written informed consent to the study participation, prior to study specific procedures * male and female (non-child-bearing potential = post-menopausal or medically adequate contraception) * ethnicity: any * age: 18 to 80 years of age * patients with histologically established diagnosis of hepatic cirrhosis and available histological material for review by the central histopathologist or a ctp score greater than or equal to 10 points plus an objective imaging study (ct or nmr scan) within 3 months of the screening visit with a confirmation of hepatic cirrhosis (scans are collected and reviewed), but excluding patients with the diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis and cystic fibrosis-associated liver disease * present ctp-class a, b or c * medically fit to undergo the protocol-defined procedures without undue risk and discomfort * predicted life-expectancy greater than or equal to 6 months by clinical judgement exclusion criteria: subjects of any of the following categories will be excluded from enrolment: * previous participation in this trial (except for scheduled re-testing in relation to technical difficulties with initial test) * 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 * any donation of germ cells, blood, organs, or bone marrow during the course of the study * history of any clinically relevant allergy (including hypersensitivity to the trial medications) * presence of clinical relevant acute or chronic infection (other than chronic viral hepatitis, if applicable) * use of confounding concomitant medication * presence or history of any end-stage (co-)morbidity (excluding the effects of hepatic cirrhosis) such as: malignancy and clinically relevant systemic diseases * 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 understand the information in this regard * primary biliary cirrhosis and primary sclerosing cholangitis * cystic fibrosis * previous liver transplantation or intended liver transplantation within 6 months after enrolment * patients having undergone previous transjugular intrahepatic portosystemic shunt (tips) or portocaval anastomosis (pca) * patients who are employees at the investigational site, relatives or spouses of the investigator * current drug, or medication abuse special restrictions for female patients: * pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation. * women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum fsh levels greater than 40 miu/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: iud, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)