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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Cirrhosis

Intervention / Treatment
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* Drug: NRL972
* Drug: NRL972
* Drug: NRL972


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females (females of non-childbearing potential or of childbearing potential while taking medically appropriate contraception) Caucasian Age: 21 - 40 years BW 50 - 100 kg BMI 20 - 26 kg.m-2 healthy based on the pre-study examination willing and able to provide informed consent Exclusion Criteria: 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 (including hypersensitivity to the trial medications) Presence of 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 (and upon admission) History of alcohol and/or drug abuse and/or daily use of > 30 gr alcohol Smoking more than 15 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 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reference<br>No pre-treatment | Drug: NRL972<br>* Single intravenous administration of 2 mg NRL972<br>|
| Experimental: T1<br>Cloxacillin pre- and co-treatment | Drug: NRL972<br>* 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.<br>|
| Experimental: T2<br>UDCA pre-treatment | Drug: NRL972<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total clearance by non-compartmental analysis. Apparent terminal disposition half-life t½ by non-compartmental analysis |  | 4 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |