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

This study has been completed.
Sponsor:
Information provided by:
Norgine
ClinicalTrials.gov Identifier:
NCT00856869
First received: March 4, 2009
Last updated: March 5, 2009
Last verified: March 2009
  Purpose

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.


Condition Intervention Phase
Hepatic Cirrhosis
Nonalcoholic Steatohepatitis
Drug: NRL972
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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.

Resource links provided by NLM:


Further study details as provided by Norgine:

Primary Outcome Measures:
  • Clearance of NRL972 after a standard meal and while fasted in healthy volunteers, patients with NASH and patients with hepatic cirrhosis. [ Time Frame: Up to 4 hours post administration of NRL972 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events and changes in physical findings from baseline [ Time Frame: Up to 4 hours post-dosing ] [ Designated as safety issue: Yes ]
  • Effects of vital signs: blood pressure, pulse rate [ Time Frame: Up to 4 hours post-dosing ] [ Designated as safety issue: Yes ]
  • Effects on electrocardiogram [ Time Frame: Up to 4 hours post-dosing ] [ Designated as safety issue: Yes ]
  • Changes in haematology, clinical chemistry, urinalysis [ Time Frame: Up to 4 hours post-dosing ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: August 2004
Study Completion Date: April 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 YM
Healthy young males
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
Experimental: 2 EM
Healthy elderly males
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
Experimental: 3 YF
Healthy young females
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
Experimental: 4 EF
Healthy elderly females
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
Experimental: 5 NASH
Patients with presumed NASH
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
Experimental: 6 CTP-A
Patients with hepatic cirrhosis CTP-class A
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal
Experimental: 7 CTP-BC
Patients with hepatic cirrhosis CTP-class B and C
Drug: NRL972
Single 2 mg intravenous injection administered once after an overnight fast and once after a standard meal

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856869

Locations
Bulgaria
UMHAPT St. Ivan Rilski's University Hospital
Sofia, Bulgaria, 1431
Sponsors and Collaborators
Norgine
Investigators
Principal Investigator: Zahariy Krastev, MD St. Ivan Rilski's University Hospital
Study Director: Hans-Jürgen Gruss, MD Norgine
  More Information

No publications provided

Responsible Party: Vice President Clinical Development, Norgine
ClinicalTrials.gov Identifier: NCT00856869     History of Changes
Other Study ID Numbers: NRL972-02/2003(ACPS)
Study First Received: March 4, 2009
Last Updated: March 5, 2009
Health Authority: Bulgaria: Ministry of Health

Additional relevant MeSH terms:
Liver Cirrhosis
Fibrosis
Fatty Liver
Liver Diseases
Digestive System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014