Evaluation of the PK of NRL972 Following Pre- and co-Administration of Ursodeoxycholic Acid and Cloxacillin

Hepatic Cirrhosis Clinical Trial

Official title:

A Single-Centre, Open, Controlled, Randomised Cross-Over Study in Healthy Male and Female Volunteers to Evaluate the Pharmacokinetics of Cholyl-Lysyl-Fluorescein (NRL972) in the Presence of Medication-Induced Changes in Cytochrome P450 or Biliary Transporter Proteins. Part B: Interaction With Ursodeoxycholic Acid and Cloxacillin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00857480
• Other study ID #: NRL972-05/2005 (IN-B)
• Status: Completed
• Phase: Phase 1
• First received: March 5, 2009
• Last updated: March 6, 2009
• Start date: June 2006
• Est. completion date: October 2006

Study information

• Verified date: March 2009
• Source: Norgine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

A study in healthy volunteers to determine whether different drugs metabolised by the liver have any effects on how NRL972 is processed within the body.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Males or females (females of non-childbearing potential or of childbearing potential while taking medically appropriate contraception)

2. Caucasian

3. Age: 21 - 40 years

4. BW 50 - 100 kg

5. BMI 20 - 26 kg.m-2

6. healthy based on the pre-study examination

7. willing and able to provide informed consent

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 300 mL within the last 3 months

4. History of any clinically relevant allergy (including hypersensitivity to the trial medications)

5. Presence of acute or chronic infection

6. Presence or history of any relevant co-morbidity

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. Presence of any relevant abnormality in the laboratory safety tests, especially low haemoglobin, increased liver enzymes

10. Positive serology for HBsAg, anti HBc and anti HCV

11. Positive HIV test

12. Positive alcohol or urine drug test on recruitment (and upon admission)

13. History of alcohol and/or drug abuse and/or daily use of > 30 gr alcohol

14. Smoking more than 15 cigarettes/day or equivalent of other tobacco products

15. Use of prohibited medication

16. Suspicion or evidence that the subject is not trustworthy and reliable

17. 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

18. Positive pregnancy test

19. Lactating

20. Not using appropriate contraception in pre-menopausal women (note: under the conditions of the present study, women using hormonal contraceptives will be informed that this method is not sufficient during the study and that further i.e. mechanical methods [condom, diaphragm with spermicidal gel] should be us

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Hepatic Cirrhosis
• Liver Cirrhosis

Intervention

Drug:
• NRL972
Single intravenous administration of 2 mg NRL972
• NRL972
Pre-treatment and co-treatment with 1 g Cloxacillin t.i.d. for three days from the morning of D-3 until the morning of Day D01 0:30 hour before the intravenous administration of NRL972.
• NRL972
Three week pre-treatment with daily doses of 500 mg b.i.d ursodeoxycholic acid from the morning of D-20 until the evening of Day D-1

Locations

Country	Name	City	State
Bulgaria	MHAPT "Zarita Johanna" University Hospital	Sofia

Sponsors (1)

Lead Sponsor	Collaborator
Norgine

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total clearance by non-compartmental analysis. Apparent terminal disposition half-life t½ by non-compartmental analysis		4 hours post-dose	No
Secondary	Non-compartmental PK-analysis based on the extensive profile (up to last quantifiable data point), the 'short' profile (over the first hour after injection), and the two-point profile based on selected data-pairs over the 1st hour after dosing		4 hours post-dose	No