Multi-national Cirrhosis Study to Characterise the Association Between the Pharmacokinetics of NRL972 and Disease Severity.

A Multi-centre, Multi-national Open Study in Patients With Hepatic Cirrhosis to Characterise the Association Between the Pharmacokinetics of NRL972 and Disease Severity.

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Cirrhosis
• Intervention / Treatment: Drug: NRL972

• Study Type: Interventional
• Enrollment (Anticipated): 1200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, D-45147
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Influence of CTP staging on the pharmacokinetics of NRL972 in patients with cirrhosis.	Single dose, 2-5 day follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Inter-subject relationship between the pharmacokinetics of NRL972 and other parameters used to define the severity of hepatic cirrhosis	2-5 days
To assess the safety and tolerability of 2mg NRL972 administered by intravenous injection to patients with hepatic cirrhosis	2-5 days

Collaborators and Investigators

• Sponsor: Norgine

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: November 19, 2008
• First Submitted That Met QC Criteria: November 19, 2008
• First Posted (Estimate): November 20, 2008

Study Record Updates

• Last Update Posted (Estimate): October 8, 2009
• Last Update Submitted That Met QC Criteria: October 7, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: NRL972-03/2006 (CIR)