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

March 5, 2009 updated by: Norgine

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Sofia, Bulgaria, 1431
        • UMHAPT St. Ivan Rilski's University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Up to 4 hours post administration of NRL972

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Adverse events and changes in physical findings from baseline
Time Frame: Up to 4 hours post-dosing
Up to 4 hours post-dosing
Effects of vital signs: blood pressure, pulse rate
Time Frame: Up to 4 hours post-dosing
Up to 4 hours post-dosing
Effects on electrocardiogram
Time Frame: Up to 4 hours post-dosing
Up to 4 hours post-dosing
Changes in haematology, clinical chemistry, urinalysis
Time Frame: Up to 4 hours post-dosing
Up to 4 hours post-dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Norgine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zahariy Krastev, MD, St. Ivan Rilski's University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2005

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2005

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 6, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 6, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NRL972-02/2003(ACPS)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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