PK of NRL972 in Patients with Nonalcoholic Steatohepatitis (NASH) and Non-Alcoholic Fatty Liver Disease (NAFLD)

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Status and phase

Completed

Phase 2

Conditions

Nonalcoholic Steatohepatitis

Non-Alcoholic Fatty Liver Disease

Treatments

Drug: NRL972

Study type

Interventional

Funder types

Industry

Identifiers

NCT00794716

NRL972-01/2007 (FLD)

Details and patient eligibility

About

This study is to evaluate the predictive value of NRL972 pharmacokinetics in the diagnosis of steatohepatitis using fatty liver disease as the comparator group. In addition, the sensitivity and specificity of NRL972 pharmacokinetics as a diagnostic tool will be compared to results from the standard laboratory tests, elastography, tests of metabolic markers and serum fibrosis markers frequently used in the evaluation of clinically predicted NAFLD patients. Patients will be included if they have clinical evidence of fatty liver disease and have been referred to the clinic for a diagnostic work-up, including a liver biopsy, blood tests and scans of the liver.

Full description

The study was conducted to describe and compare the plasma pharmacokinetics of NRL972 after a 15-second intravenous (i.v.) injection of 2 mg NRL972 against the diagnostic assessment based on liver biopsy in patients with clinically suspected NAFLD. A particular focus was to separate simple fatty liver disease (non-NASH) from non-alcoholic steatohepatitis (NASH) with or without cirrhosis (defined as advanced fibrosis: ≥F3) in a population likely to present with NAFLD.

The study evaluated the predictive value of NRL972 pharmacokinetics in the diagnosis of NASH using fatty liver disease (non-NASH) as the comparator group in a population of clinically suspected NAFLD patients based on histological evaluation. The sensitivity and specificity of NRL972 pharmacokinetics as a diagnostic was compared to that of results from the standard laboratory tests, clinical features, elastography assessments for liver stiffness and tests of metabolic markers, serum fibrosis markers and established disease scores frequently used in the evaluation of NAFLD.

The study also provided information on the safety and tolerability of i.v. doses of NRL972 under these conditions.

Enrollment

125 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Subjects meeting the following conditions will be eligible for enrollment:

Males or females (females of non-child-bearing potential or of child-bearing potential while taking medically appropriate contraception)
Any ethnicity
Age: 18 to 80 years of age
Clinical evidence of non-alcoholic liver disease requiring the conduct of a liver biopsy for the diagnosis of NAFLD and/or staging of disease severity
Willing and able to provide informed consent

Exclusion criteria

Subjects fulfilling any of the following criteria will be excluded from enrollment:

General - all subjects

Presence of acute or chronic viral hepatitis confirmed by serology
Clinical signs of significant cholestasis
Liver impairment due to space-occupying processes (e.g. carcinoma)
Liver transplant recipient or patient scheduled for liver transplantation
Clinically evident rapidly deteriorating hepatic function
Significant bleeding diathesis
Esophageal bleeding within the 8 weeks prior to study entry
Presence of any contraindications for the conduct of the planned liver biopsy (e.g. allergy to lidocaine, coagulopathy with <100 x109/L thrombocytes and/or INR >1.3
History of any allergic reaction to fluorescein
Presence of any acute infection
Previous participation in this trial
Having received any investigational drug or treatment within 30 days prior to study entry or requiring a concurrent treatment with any other experimental drug or treatment
Uncontrolled hypo- or hypertension (treated or untreated) with resting systolic blood pressure >160 or < 90 mmHg, diastolic blood pressure >95 or < 50 mmHg
Clinically relevant abnormal laboratory values indicating end-stage renal, pulmonary or cardiac disease
Known HIV infection
Concurrent alcohol use of more than 14 drinks (140g ethanol) for men and 7 drinks (70g ethanol) for women per week (each drink is counted as 10g ethanol)
History of drug or alcohol abuse within 2 months prior to dosing
Use of prohibited medication (section 4.8)
Donation of blood during the last 60 days or a history of blood loss exceeding 300 mL within the last 3 months
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 understand the information in this regard
Significant side effects prior to the liver biopsy (e.g. anxiety requiring pre-medication) or after the biopsy (e.g. pain requiring i.v. pain medication, bleeding re-quiring medical intervention)