Clearance of NRL972 in Patients With Cirrhosis and in Healthy Volunteers

Study Overview
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Brief Summary
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A study in healthy volunteers and patients with liver cirrhosis to assess the effects of age, gender, and stable liver disease on the clearance of cholyl-lysyl-fluorescein (NRL972)

Official Title
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A Study in Healthy Volunteers and Patients With Liver Cirrhosis to Assess the Effects of Age, Gender, and Stable Liver Disease on the Clearance of Cholyl-Lysyl-Fluorescein (NRL972) as an in-Vivo Marker of Liver Function in Man

Conditions
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Hepatic Cirrhosis

Intervention / Treatment
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* Drug: NRL972
* Drug: NRL972
* Drug: NRL972
* Drug: NRL972
* Drug: NRL972
* Drug: NRL972


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects meeting the following conditions will be eligible for enrolment: General - all subjects Males or females (females of non-child-bearing potential or of child-bearing potential while taking medically appropriate contraception) Caucasian BMI: between 19 and 34 kg.m-2 BW: between 45 and 110 kg willing and able to provide informed consent Healthy volunteers (group N) Age: 18 - 40 years (inclusive) and > 60 years Assessed as healthy based on the pre-study examination Hepatic cirrhosis Age: 18 - 75 years stable compensated liver cirrhosis (cryptogenic, posthepatic, alcoholic) with histo-logical or macroscopic (e.g. laparascopy, biopsy, ultrasound sonography or other adequate imaging techniques) confirmation Exclusion Criteria: Subjects of any of the following categories will be excluded from enrolment: General - all subjects Previous participation in the trial 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 History of any clinically relevant allergy Presence of acute or chronic infection Uncontrolled diabetes mellitus Resting systolic blood pressure > 160 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg Clinically relevant ECG-abnormalities, prolonged QTc with > 450 msec in males and > 460 msec in females in particular Positive HIV test Positive alcohol or urine drug test on recruitment Daily use of > 30 gr alcohol Smoking more than 15 cigarettes/day or equivalent of other tobacco products Use of prohibited medication 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 under-stand the information in this regard General - all females Positive pregnancy test Lactating Not using appropriate contraception in premenopausal women All healthy subjects Presence or history of any relevant comorbidity Presence of any relevant abnormality in the laboratory safety tests, especially low Hemoglobin, increased liver enzymes, reduced serum creatinine Positive serology for HBsAg, anti HBc and anti HCV History of alcohol and/or drug abuse Patients with hepatic disease Biliary liver cirrhosis Liver impairment due to space-occupying processes (e.g. carcinoma) State after liver transplantation or patient scheduled for liver transplantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 YM<br>Healthy young males | Drug: NRL972<br>* Single intravenous dose of 2 mg NRL972<br>|
| Experimental: 2 EM<br>Healthy elderly males | Drug: NRL972<br>* Single intravenous dose of 2 mg NRL972<br>|
| Experimental: 3 YF<br>Healthy young females | Drug: NRL972<br>* Single intravenous dose of 2 mg NRL972<br>|
| Experimental: 4 EF<br>Healthy elderly females | Drug: NRL972<br>* Single intravenous dose of 2 mg NRL972<br>|
| Experimental: 5 CTP-A<br>Patients with hepatic cirrhosis CTP-class A | Drug: NRL972<br>* Single intravenous dose of 2 mg NRL972<br>|
| Experimental: 6 CTP-BC<br>Patients with hepatic cirrhosis CTP-class B and C | Drug: NRL972<br>* Single intravenous dose of 2 mg NRL972<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of NRL972 in healthy subjects and patients with hepatic cirrhosis |  | Up to 4 hrs post administration of NRL972 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and changes in physical findings from baseline |  | Up to 4 hours post-dosing | 
| Effects on vital signs: blood pressure, pulse rate |  | Up to 4 hours post-dosing | 
| Effects on electrocardiogram |  | Up to 4 hours post-dosing | 
| Changes in haematology, clinical chemistry, urinalysis |  | Up to 4 hours post-dosing |