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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00857480
Recruitment Status : Completed
First Posted : March 6, 2009
Last Update Posted : March 9, 2009
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Brief 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.

Condition or disease Intervention/treatment Phase
Hepatic Cirrhosis Drug: NRL972 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Study Start Date : June 2006
Actual Primary Completion Date : August 2006
Actual Study Completion Date : October 2006

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Arm Intervention/treatment
Experimental: Reference
No pre-treatment
Drug: NRL972
Single intravenous administration of 2 mg NRL972

Experimental: T1
Cloxacillin pre- and co-treatment
Drug: 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.

Experimental: T2
UDCA pre-treatment
Drug: 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

Primary Outcome Measures :
  1. Total clearance by non-compartmental analysis. Apparent terminal disposition half-life t½ by non-compartmental analysis [ Time Frame: 4 hours post-dose ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: 4 hours post-dose ]

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Ages Eligible for Study:   21 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00857480

MHAPT "Zarita Johanna" University Hospital
Sofia, Bulgaria, 1431
Sponsors and Collaborators
Study Director: Hans-Jürgen Gruss, MD Norgine
Principal Investigator: Emil Gatchev, PD Dr med MHAPT "Zarita Johanna" University Hospital

Responsible Party: Vice President Clinical Development, Norgine Ltd Identifier: NCT00857480     History of Changes
Other Study ID Numbers: NRL972-05/2005 (IN-B)
First Posted: March 6, 2009    Key Record Dates
Last Update Posted: March 9, 2009
Last Verified: March 2009

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents
Anti-Bacterial Agents
Anti-Infective Agents