Clearance of NRL972 in Patients With Cirrhosis and in Healthy Volunteers

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

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)

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1431
    • UMHAPT St Ivan Rilski's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects meeting the following conditions will be eligible for enrolment:

General - all subjects

1. Males or females (females of non-child-bearing potential or of child-bearing potential while taking medically appropriate contraception)
2. Caucasian
3. BMI: between 19 and 34 kg.m-2
4. BW: between 45 and 110 kg

5. willing and able to provide informed consent

   Healthy volunteers (group N)

6. Age: 18 - 40 years (inclusive) and > 60 years

7. Assessed as healthy based on the pre-study examination

   Hepatic cirrhosis

8. Age: 18 - 75 years
9. 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

1. Previous participation in the trial
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. History of any clinically relevant allergy
5. Presence of acute or chronic infection
6. Uncontrolled diabetes mellitus
7. Resting systolic blood pressure > 160 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg
8. Clinically relevant ECG-abnormalities, prolonged QTc with > 450 msec in males and > 460 msec in females in particular
9. Positive HIV test
10. Positive alcohol or urine drug test on recruitment
11. Daily use of > 30 gr alcohol
12. Smoking more than 15 cigarettes/day or equivalent of other tobacco products
13. Use of prohibited medication
14. Suspicion or evidence that the subject is not trustworthy and reliable

15. 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

16. Positive pregnancy test
17. Lactating

18. Not using appropriate contraception in premenopausal women

    All healthy subjects

19. Presence or history of any relevant comorbidity
20. Presence of any relevant abnormality in the laboratory safety tests, especially low Hemoglobin, increased liver enzymes, reduced serum creatinine
21. Positive serology for HBsAg, anti HBc and anti HCV

22. History of alcohol and/or drug abuse

    Patients with hepatic disease

23. Biliary liver cirrhosis
24. Liver impairment due to space-occupying processes (e.g. carcinoma)
25. State after liver transplantation or patient scheduled for liver transplantation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Adverse events and changes in physical findings from baseline	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
Effects on vital signs: blood pressure, pulse rate	Up to 4 hours post-dosing

Collaborators and Investigators

• Sponsor: Norgine
• Investigators: Principal Investigator: Zahariy Krastev, MD, St Ivan Rilski's University Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: March 4, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (Estimate): March 6, 2009

Study Record Updates

• Last Update Posted (Estimate): March 6, 2009
• Last Update Submitted That Met QC Criteria: March 5, 2009
• Last Verified: March 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: NRL972-01/2005 (ACPS)