Clearance of NRL972 in Patients With Cirrhosis, Nonalcoholic Steatohepatitis (NASH) and in Healthy Volunteers

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

A Study in Healthy Volunteers and Patients With Liver Cirrhosis and Non-Alcoholic Steatohepatitis (NASH) to Assess the Effects of Age, Gender, Chronic Liver Disease, and Prandial Effects on the Clearance of Cholyl-Lysyl-Fluorescein (NRL972) an an in-Vivo Marker of Liver Function in Man.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00856869
• Other study ID #: NRL972-02/2003(ACPS)
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 4, 2009
• Last updated: March 5, 2009
• Start date: August 2004
• Est. completion date: April 2005

Study information

• Verified date: March 2009
• Source: Norgine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The study was conducted to describe and compare the plasma pharmacokinetics of NRL972 administered after a standard meal and while fasted in patients with hepatic cirrhosis (Child-Turcotte-Pugh [CTP] class A-C), NASH, young and elderly healthy males, and young and elderly healthy females, to assess the effects of liver dysfunction, gender, age and prandial intestinal hyperaemia on the clearance of NRL972. In addition, the study was to provide information on the safety and tolerability of repeated intravenous doses of NRL972 in these populations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: April 2005
• Est. primary completion date: February 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

General - all subjects

1. Males or females (females of non-childbearing potential or of childbearing 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) e.g. > 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 Nonalcoholic steatohepatitis (NASH)

10. Age: 18 - 75 years

11. Diagnosis of NASH confirmed by liver biopsy

Exclusion Criteria:

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 450 mL within the last 3 months

4. History of any clinically relevant allergy

5. Uncontrolled diabetes mellitus or any further intolerability of the Galactose test

6. Presence of acute or chronic infection

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. Clinically relevant ECG-abnormalities that constitute a contraindication for the Lido-cain-MEG'-X-test

10. Positive HIV test

11. Positive alcohol or urine drug test on recruitment

12. Daily use of > 30 gr alcohol

13. Smoking more than 15 cigarettes/day or equivalent of other tobacco products

14. Use of prohibited medication

15. Suspicion or evidence that the subject is not trustworthy and reliable

16. 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

17. Positive pregnancy test

18. Lactating

19. Not using appropriate contraception in premenopausal women All healthy subjects

20. Presence or history of any relevant comorbidity (list of past and present diseases will be reviewed by an expert panel)

21. Presence of any relevant abnormality in the laboratory safety tests, especially low haemoglobin, increased liver enzymes, reduced serum creatinine (laboratory test abnormalities will be reviewed by an expert panel)

22. Positive serology for HBsAg, anti HBc and anti HCV

23. History of alcohol and/or drug abuse.

Patients with hepatic disease

24. Biliary liver cirrhosis

25. Liver impairment due to space-occupying processes (e.g. carcinoma)

26. State after liver transplantation or patient scheduled for liver transplantation

27. Fluctuating or rapidly deteriorating hepatic function

28. Significant bleeding diathesis

29. Oesophageal bleeding within the last 8 weeks before study entry

30. Ascites > 6 L on abdominal US

31. Number Connection test: time to connect 25 consecutive numbers > 30 sec

32. Presence or history of any relevant comorbidity other than hepatic disease (list of past and present diseases will be reviewed by an expert panel)

33. Clinically relevant abnormal laboratory values other than those associated or sufficiently explained by the existing liver disease (laboratory test abnormalities will be reviewed by an expert panel)

34. History of drug or alcohol abuse within 2 months prior to dosing

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Fatty Liver
• Hepatic Cirrhosis
• Liver Cirrhosis
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
• NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal

Locations

Country	Name	City	State
Bulgaria	UMHAPT St. Ivan Rilski's University Hospital	Sofia

Sponsors (1)

Lead Sponsor	Collaborator
Norgine

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance of NRL972 after a standard meal and while fasted in healthy volunteers, patients with NASH and patients with hepatic cirrhosis.		Up to 4 hours post administration of NRL972	No
Secondary	Adverse events and changes in physical findings from baseline		Up to 4 hours post-dosing	Yes
Secondary	Effects of vital signs: blood pressure, pulse rate		Up to 4 hours post-dosing	Yes
Secondary	Effects on electrocardiogram		Up to 4 hours post-dosing	Yes
Secondary	Changes in haematology, clinical chemistry, urinalysis		Up to 4 hours post-dosing	Yes