Effect of Chronic Viral Hepatitis on the Pharmacokinetics of NRL972.

This study has been completed.
Sponsor:
Information provided by:
Norgine
ClinicalTrials.gov Identifier:
NCT00915057
First received: June 3, 2009
Last updated: December 21, 2009
Last verified: December 2009
  Purpose

Little is known about the nature and extent of the disturbance in hepatic function and biliary hepatic clearance in chronic viral hepatitis, while the course of this disease, the functional implications and response to treatment are difficult to predict. This study aims to assess this in patients with chronic viral hepatitis B (CHB) and chronic viral hepatitis C (CHC) who are eligible for treatment in accordance with the established consensus guidelines in the involved countries. The pharmacokinetics of NRL972 will be determined at baseline (within one month of starting treatment), at 3-monthly intervals during treatment, for up to 12 months (or at the end of treatment), and at 3 and 6 months after the end on treatment. This will provide a clearer understanding regarding the use of the pharmacokinetics of NRL972 in detecting changes in biliary clearance during and after treatment for CHB and CHC.


Condition Intervention Phase
Hepatitis, Viral, Human
Drug: NRL972
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: An Open Study to Investigate the Effects of Chronic Viral Hepatitis B or C on the Pharmacokinetics of Cholyl-lysyl-fluorescein (NRL972) Before, During and After Standard Treatment.

Resource links provided by NLM:


Further study details as provided by Norgine:

Primary Outcome Measures:
  • Pharmacokinetics of NRL972 [ Time Frame: Up to one hour post-dosing ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2009
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NRL972
Single 2mg intravenous dose of NRL972, administered on up to seven occasions
Drug: NRL972
Single dose of NRL972 administered at baseline, at 3-monthly intervals during treatment for up to 12 months (or the end of treatment) and at 3 and 6 months after the end of treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Chronic viral hepatitis B

  • Adult, male or female, age ≥ 18 years and < 65 years
  • Body weight (BW) : 45 - 110 kg
  • Body mass index (BMI) : 18 - 30 kg.m-2
  • HBV Serology: HBsAg+ for ≥ 6 months (at the time of application for treatment)
  • Serum ALT ≥ 1.5 times ULN ≥ 6 months (at the time of application for treatment)
  • Positive liver biopsy within 24 months before screening visit
  • Positive biopsy with signs of active disease (any level of activity by Knodell, METAVIR or ISHAK)
  • HBV DNA counts determined by quantitative PCR: ≥ 20,000 IU/mL ALT < 10 times ULN
  • HIV-Ab negative
  • Non-cirrhotic liver disease (on histology within 24 months before screening visit)
  • Not having been treated for chronic viral hepatitis previously ("de novo" i.e. "naïve")
  • Eligible for treatment of chronic viral hepatitis in accordance with the national consensus guidelines pertinent to the country and site of conduct of the trial
  • Willing and able to provide informed consent

Chronic viral hepatitis C

  • Adult, male or female, age ≥ 18 years and < 65 years
  • Body weight (BW) : 45 - 110 kg
  • Body mass index (BMI) : 18 - 30 kg.m-2
  • HCV-Ab+ for ≥ 6 months (at the time of application for treatment)
  • HCV RNA counts > 10,000 U/L by quantitative PCR assay within the last 6 months (at the time of application for treatment)
  • Positive liver biopsy within 24 months before application for treatment
  • Positive biopsy with signs of fibrotic disease (levels of fibrosis METAVIR ≥ F1 or ISHAK ≥ F2)
  • ALT < 10 times ULN
  • HIV-Ab negative
  • Non-cirrhotic liver disease (on histology within 24 months before screening visit)
  • Not having been treated for chronic viral hepatitis previously ("de novo" i.e. "naïve")
  • Eligible for treatment of chronic viral hepatitis in accordance with the national consensus guidelines pertinent to the country and site of conduct of the trial
  • Willing and able to provide informed consent

Chronic viral hepatitis C plus chronic viral hepatitis B

  • Patients with combined CHB and CHC will be managed (in terms of eligibility and standard treatment in accordance with the hepatitis type with predominant viral replication.

Exclusion Criteria:

Trial specific criteria: CHB, CHC & CHB+CHC

  • Previous participation in the trial
  • Participation in any other clinical trial within 30 days of entry to this protocol
  • Treatment with any investigational drug within 30 days of entry to this protocol
  • Non-response to previous treatment for chronic viral hepatitis
  • Relapse after previous treatment for chronic viral hepatitis
  • Any other known cause of liver disease other than chronic viral hepatitis B and/or C, including but not limited to hepatitis D, haemochromatosis, alpha1-antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, drug-related liver disease
  • Evidence of advanced liver disease, such as history or presence of ascites, bleeding varices, encephalopathy
  • Patients with organ transplants
  • Hypersensitivity to prospective standard treatment
  • Any relevant co-morbidity, for instance, but not limited to:
  • Limiting uncompensated psychiatric condition (e.g. severe depression, or a history of severe psychiatric disorder)
  • CNS trauma or seizure disorder requiring medication
  • Significant cardiovascular dysfunction within the past 6 months (e.g. angina, congestive cardiac failure, recent myocardial infarction, severe hypertension or significant arrhythmia)
  • Patients with an ECG showing clinically significant abnormalities
  • Poorly controlled diabetes mellitus
  • Patients on haemodialysis
  • Daily use of > 40 g alcohol
  • Positive alcohol test at SCR-visit
  • Evidence or suspicion of social drug abuse
  • Positive drug test at SCR-visit
  • 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

Criteria specifically related to the standard treatment of chronic viral hepatitis

  • Relevant clinical laboratory test abnormalities, for instance, but not limited to:

Haemoglobin (Hgb) <11 g dL-1 for women and <13 g dL-1 for men

White Blood Cell count (WBC) < 3,000 10 exp9/mL

Granulocyte count < 1,500 10 exp9/mL

Lymphocyte count < 500 10 exp9/mL

Platelets < 75,000 10 exp9/mL

Prothrombin time - INR > 1.4

Bilirubin > 25 micromol/L (except in functional hyperbilirubinaemia)

Albumin < 35 g/L

Serum creatinine > 133 micromol/L

Fasting blood glucose > 7.4 mmol/L for non-diabetic patients

HbA1c > 7% for diabetic patients

Positive auto-immune antibodies

TSH outside the normal range (for patients intended for interferon)

  • Relevant co-morbidity, for instance, but not limited to:

Limiting uncompensated chronic pulmonary disease (e.g. chronic obstructive pulmonary disease)

Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids

Gout - (for patients intended for interferon)

Immunologically mediated disease (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, cryoglobulinaemia with vasculitis) - (for patients intended for interferon)

Patients with clinically significant retinal abnormalities - (for patients intended for interferon)

All females

  • Positive pregnancy test
  • Lactating
  • Not using medically appropriate contraception and/or not willing to maintain such contraception during the treatment of chronic viral hepatitis and up to 6 months thereafter
  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: NCT00915057

Locations
Bulgaria
MHAT Sveti Ivan Rilski EAD
Sofia, Bulgaria
Romania
Clinical Institute Fundeni
Bucharest, Romania
Emergency Country Hospital Cluj
Cluj, Romania
Private Clinic Algomed SRL
Timisoara, Romania
Sponsors and Collaborators
Norgine
Investigators
Study Director: Hans-Jürgen Gruss, MD Norgine
  More Information

No publications provided

Responsible Party: Vice President Clinical Development, Norgine
ClinicalTrials.gov Identifier: NCT00915057     History of Changes
Other Study ID Numbers: NRL972-09/2008 (CHBC)
Study First Received: June 3, 2009
Last Updated: December 21, 2009
Health Authority: Romania: National Medicines Agency
Bulgaria: Bulgarian Drug Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Viral, Human
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepatitis B
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic

ClinicalTrials.gov processed this record on July 20, 2014