Reproducibility of Child-Turcotte-Pugh (CTP) Rating and NRL972 Pharmacokinetics in Patients With Cirrhosis

Inclusion criteria

• Able to give written Informed Consent.
• Gender: male and female (non-childbearing potential = postmenopausal or medically adequate contraception).
• Ethnicity: Any.
• Age: 18 to 80 years of age.
• Patient volunteers with a diagnosis of clinically stable hepatic cirrhosis with a CTP class A, B and C but excluding patient volunteers with the diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis and cystic fibrosis-associated liver disease.
• No previous liver transplantation or intended liver transplantation within the next 6 months after enrollment.
• No previous transjugular intrahepatic portosystemic shunt (TIPS) or portocaval anastomosis (PCA).
• Medically fit to undergo the protocol-defined procedures without undue risk and discomfort.
• No previous participation in a study with an investigational product within 90 days prior to enrolment except epidemiologic or observational studies.

Exclusion criteria

• Previous participation in this trial (except for scheduled re-testing in relation to technical difficulties with initial test or rescreening).
• Donation of blood during the last 60 days or a history of excessive blood loss within the last 3 months, assessed using clinical judgement.
• 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 IMP).
• Presence of clinical relevant acute or chronic infection (other than chronic viral hepatitis, if applicable).
• Presence of hepatic encephalopathy at grades 3 or 4
• Unstable clinical presentation of hepatic cirrhosis (not allowing completion of participation in the study within 6 weeks).
• Use of confounding concomitant medication (see Section 7.5.7).
• Presence or history of any end-stage (co-)morbidity (excluding the effects of hepatic cirrhosis) such as: malignancy and clinically relevant systemic diseases.
• Presence of primary and/or hepatic malignancy.
• Suspicion or evidence that the patient volunteer is not trustworthy and reliable.
• Suspicion or evidence that the patient volunteer 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.
• Patient volunteers who are employees at the investigational site, relatives or spouses of the investigator.
• Current drug or medication abuse.

Special restrictions for female patient volunteers:

• 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 childbearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career or lifestyle precludes intercourse with a male partner and women whose partners have been sterilised 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 > 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 sterilisation (e.g., bilateral tubal ligation, vasectomy)
• hormonal contraception (implantable, patch, oral), and
• double-barrier methods (any double combination of: an intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap).