Clearance of NRL972 in Patients With Cirrhosis and in Healthy Volunteers

Norgine

Status and phase: Completed; Phase 1

Conditions: Hepatic Cirrhosis

Treatments: Drug: NRL972

Study type: Interventional

Funder types: Industry

Identifiers

NCT00856713

NRL972-01/2005 (ACPS)

Details and patient eligibility

About

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)

Enrollment: 72 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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72 participants in 6 patient groups

1 YM

Experimental group

Description:

Healthy young males

Treatment:

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

2 EM

Experimental group

Description:

Healthy elderly males

Treatment:

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

3 YF

Experimental group

Description:

Healthy young females

Treatment:

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

4 EF

Experimental group

Description:

Healthy elderly females

Treatment:

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

5 CTP-A

Experimental group

Description:

Patients with hepatic cirrhosis CTP-class A

Treatment:

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

6 CTP-BC

Experimental group

Description:

Patients with hepatic cirrhosis CTP-class B and C

Treatment:

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972

Drug: NRL972