An open study to investigate the effects of chronic hepatitis B or C on the pharmacokinetics of cholyl-lysyl-fluorescein (NRL972) before, during and after standard treatment - NRL972 in chronic heptatitis
- Conditions
- MedDRA version: 9.1Level: LLTClassification code 10009213Term: Cirrhosis of liverIn-vivo diagnostic marker for liver dysfunction.
- Registration Number
- EUCTR2008-003547-36-BG
- Lead Sponsor
- orgine Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
Chronic 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
Not having been treated for chronic hepatitis previously (de novo i.e. naïve)
Eligible for treatment of chronic 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 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 histology)
Not having been treated for chronic hepatitis previously (de novo i.e. naïve)
Eligible for treatment of chronic 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
A. General criteria
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 hepatitis
Relapse after previous treatment for chronic hepatitis
Any other known cause of liver disease other than chronic 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
B. Exclusion criteria related to the medicaiton used for the standard treatment of chronic 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) < 3,000 109/mL
- Granulocyte count < 1,500 109/mL
- Lymphocyte count < 500 109/mL
- Platelets < 75,000 109/mL
- Prothrombin time – INR > 1.4
- Bilirubin > 25 ?mol/L (except in functional hyperbilirubinaemia)
- Albumin < 35 g/L
- Serum creatinine > 133 ?mol/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)
C. Criteria applicable to all female subjects:
Positive pregnancy test
Lactating
Not using medically appropriate contraception and/or not willing to maintain such contraception during the treatment of chronic hepatitis and up to 6 months thereafter
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Quantification of liver function by NRL972-pharmacokinetics before, during and after standard treatment of chronic hepatitis B and C;Secondary Objective: Safety and tolerability of repeated single doses of 2 mg NRL972 before, during and after standard treatment of chronic hepatitis;Primary end point(s): Pharmacokinetics of NRL972 in terms of the C(30):C(10)-ratio, clearance (CL & CL/BW), and apparent terminal disposition half-life (t1/2) and urinary excretion of NRL972
- Secondary Outcome Measures
Name Time Method