Sensitivity of Alternative NRL972 Detection Methods in Healthy Subjects

Investigation of the Sensitivity of Different Methods to Detect NRL972 in Healthy Volunteers During and After a 2-hour Intravenous Infusion of 10 and 30mg NRL972

The disposition of NRL972 after a 15-second intravenous injection of 2 mg NRL972 is distinctly slower in patients with hepatic cirrhosis and acute hepatitis than in healthy control subjects. NRL972 appears to be a suitable investigational marker of hepatic transporter clearance dysfunction.

Although the pharmacokinetics of NRL972 provide a reliable differentiation between subject groups, this approach relies on precisely timed sampling of venous blood, cautious preparation, handling and on-site storage of plasma samples, the transfer of samples to a central laboratory for analysis, and the availability of a validated assay procedure.

For these reasons, there is interest in developing and validating alternative methods for determining the concentration of NRL972 in venous blood. Two such methods have been developed to date, but their utility in determining NRL972 pharmacokinetics has yet to be established.

Study Overview

• Status: Completed
• Conditions: Cirrhosis
• Intervention / Treatment: Other: NRL972

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Balatonfüred, Hungary, H-8230
    • Phase I-II study clinical of the Drug Research Center Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects meeting the following conditions will be eligible for enrolment:

• Males or females (females of non-childbearing potential or of childbearing potential while taking medically appropriate contraception)
• Caucasian
• Age: 20 to 45 years
• BMI 20 - 26 kg.m-2
• Healthy based on the pre-study examination
• Suitable veins for easy cannulation
• Willing and able to provide informed consent

Exclusion Criteria:

Subjects of any of the following categories will be excluded from enrolment:

General - all subjects

• Previous participation in the trial
• Participant in any other trial during the last 90 days
• Donation of blood during the last 60 days or a history of blood loss exceeding 300 mL within the last 3 months
• History of any clinically relevant allergy
• Presence of any acute or chronic infection
• Presence or history of any relevant co-morbidity
• Resting systolic blood pressure > 160 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg
• Clinically relevant ECG-abnormalities, prolonged QTc with > 450 msec in males and > 460 msec in females in particular
• Presence of any relevant abnormality in the laboratory safety tests, especially low haemoglobin, increased liver enzymes
• Positive serology for HBsAg, anti HBc and anti HCV
• Positive HIV test
• Positive alcohol or urine drug test on recruitment
• History of alcohol and/or drug abuse and/or daily use of > 30 g alcohol
• Smoking more than 10 cigarettes/day or equivalent of other tobacco products
• 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 understand the information in this regard

General - all females

• Positive pregnancy test
• Lactating
• Not using appropriate contraception in premenopausal women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Method A; First experimental detection method	Other: NRL972; Two-hour intravenous infusion of 5 and 15 mg per hour
Other: Method B; Second experimental detection method	Other: NRL972; Two-hour intravenous infusion of 5 and 15 mg per hour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ratios of the plasma concentration at 30 minutes post-infusion to the concentrations at 10 and 15 minutes post-infusion	Up to 4 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	Up to 4 hours post-dose
Vital signs	Up to 4 hours post-dose
ECG	Up to 4 hours post-dose
Clinical laboratory blood tests	Up to 4 hours post-dose

Collaborators and Investigators

• Sponsor: Norgine
• Investigators: Principal Investigator: Eva Peterfai, MD, Drug Research Center Ltd.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: July 13, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 16, 2010

Study Record Updates

• Last Update Posted (Estimate): June 10, 2015
• Last Update Submitted That Met QC Criteria: June 9, 2015
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis
• Other Study ID Numbers: NRL972-01/2010 (AMET)