A multi-centre, multi-national open study in patients with hepatic cirrho-sis to characterise the association between the pharmacokinetics of NRL972 and disease severity

• Conditions: Hepatic cirrhosis.; MedDRA version: 9.1Level: LLTClassification code 10019641Term: Hepatic cirrhosis

• Registration Number: EUCTR2007-002404-18-BG
• Lead Sponsor: orgine Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08-01
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

Subjects meeting the following conditions will be eligible for enrolment:
1.Patient has given his/her written informed consent to the study participation, prior to study specific procedures.
2. Male and female (non-child-bearing potential = post-menopausal or medically adequate contraception).
3. Ethnicity: any.
4. Age: 18 to 80 years of age.
5. Patients with histologically established diagnosis of hepatic cirrhosis and available histological material for review by the central histopathologist or a CTP score = 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
6. Present CTP-class A, B or C
7. Medically fit to undergo the protocol-defined procedures without undue risk and discomfort
8. Predicted life-expectancy of greater than or equal to 6 months by clinical judgement

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects of any of the following categories will be excluded from enrolment:
1. Previous participation in this trial (except for scheduled re-testing in relation to technical difficulties with initial test).
2. Participant in any other trial during the last 90 days.
3. Donation of blood during the last 60 days or a history of blood loss exceeding 300 mL within the last 3 months.
4. Any donation of germ cells, blood, organs, or bone marrow during the course of the study.
5. History of any clinically relevant allergy (including hypersensitivity to the trial medications).
6. Presence of clinical relevant acute or chronic infection (other than chronic viral hepatitis, if applicable).
7. Use of confounding concomitant medication (see Section 7.5.7).
8. Presence or history of any end-stage (co-)morbidity (excluding the effects of hepatic cirrhosis) such as: malignancy and clinically relevant systemic diseases
9. Suspicion or evidence that the subject is not trustworthy and reliable.
10. Suspicion or evidence that the subject is not able to make a free consent or to understand the information in this regard
11. Primary biliary cirrhosis and primary sclerosing cholangitis
Cystic fibrosis
12. Previous liver transplantation or intended liver transplantation within 6 months after enrolment
13. Patients having undergone previous transjugular intrahepatic portosystemic shunt (TIPS) or portocaval anastomosis (PCA)
14. Patients who are employees at the investigational site, relatives or spouses of the investigator
15. Current drug, or medication abuse
16. 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 >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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Final proof of the influence of CTP staging on the pharmacokinetics of NRL972 in cirrhosis (using the C(30):C(10) two-point recovery ratio for NRL972 as the primary endpoint);Secondary Objective: To: <br>Investigate the between-subject relationship between the pharmacokinetics of NRL972 and the different reference criteria (such as: extended CTP, multifactorial matrix parameters) that express the severity of hepatic cirrhosis.<br>Compare the two-point analysis of NRL972 against the 60 minutes short pharmacokinetic profile in patients with histological confirmed hepatic cirrhosis.<br>Describe the safety and tolerability of a single dose of 2 mg NRL972 by i.v. injection in patients with different stages of hepatic cirrhosis.<br>;Primary end point(s): The primary variable of the study is the 2-point fractional recovery C(30):C(10) concentration ratio of NRL972 (where C(ti)=concentration at ti minutes after i.v. injection of NRL972).