E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019641 |
E.1.2 | Term | Hepatic cirrhosis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
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E.2.2 | Secondary objectives of the trial |
To: 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. Compare the two-point analysis of NRL972 against the 60 minutes short pharmacokinetic profile in patients with histological confirmed hepatic cirrhosis. 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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).
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E.5 End points |
E.5.1 | 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). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |