Clinical trial NCT00794482: Multi-national Cirrhosis Study to Characterise the Association Between the Pharmacokinetics of NRL972 and Disease Severity.
Official title: A Multi-centre, Multi-national Open Study in Patients With Hepatic Cirrhosis to Characterise the Association Between the Pharmacokinetics of NRL972 and Disease Severity.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatic Cirrhosis
Lead sponsor: Norgine
Sponsor class: INDUSTRY
First posted: 2008-11-20
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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)

Primary outcomes:
measure: Influence of CTP staging on the pharmacokinetics of NRL972 in patients with cirrhosis.
timeFrame: Single dose, 2-5 day follow-up
Secondary outcomes:
measure: Inter-subject relationship between the pharmacokinetics of NRL972 and other parameters used to define the severity of hepatic cirrhosis
timeFrame: 2-5 days
measure: To assess the safety and tolerability of 2mg NRL972 administered by intravenous injection to patients with hepatic cirrhosis
timeFrame: 2-5 days
Other outcomes:
Locations:
city: Essen
country: Germany
facility: University Hospital
Study officials:
References: