Influence of the OATP1B1 genotype on the hepatic uptake of Primovist® in healthy volunteers and in patients with liver disease

• Conditions: The trial will be performed in 32 healthy subjects and in 60 patients with a liver disease subjected to MR imaging; MedDRA version: 8.1Level: LLTClassification code 10028049Term: MRI

• Registration Number: EUCTR2006-005249-13-DE
• Lead Sponsor: Department of Clinical Pharmacology, University of Greifswald

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-25
• Last Update Posted: 29 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion criteria – healthy volunteers
*age:18 - 45 years
*sex:male and female
*ethnic origin:white
*body weight:? 19 kg/m² and ? 27 kg/m²
*good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
*written informed consent

Inclusion criteria – patients
*age:18 - 65 years
*sex:male and female
*ethnic origin:white
*any liver disease (e.g. primary liver tumor, metastatic liver disease, liver cirrhosis, steatosis hepatis) which is subjected to MRI diagnostics
*written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria – healthy volunteers
•weight less than 45 kg
•claustrophobia
•cardiac pacemakers, metallic implants or metal-containing tatoos
•history of allergic reactions
•known hypersensitivity to the study medication or to their adjuvants
•existing cardiac or hematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics
•existing hepatic and renal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics
•existing gastrointestinal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics
•acute or chronic diseases which could affect drug metabolism or elimination
•history of any serious psychological disorder
•drug or alcohol dependence
•positive drug or alcohol screening
•smokers of 10 or more cigarettes per day
•positive anti-HIV-test, HBs-Ag-test or anti-HCV-test
•volunteers who are on a diet which could affect the pharmacokinetics of the drug
•heavy tea or coffee drinkers (more than 1L per day)
•lactation and pregnancy test positive or not performed
•volunteers suspected or known not to follow instructions
•volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
•volunteers liable to orthostatic dysregulation, fainting, or blackouts
•participation in a clinical trial during the last 3 months prior to the start of the study
•less than 14 days after last acute disease
•any systemically available medication within 4 weeks prior to the intended first administration unless because of the terminal elimination half-life complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
•repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)
•intake of grapefruit containing food or beverages within 7 days prior to administration

5.4Exclusion criteria – patients
•weight less than 45 kg
•claustrophobia
•cardiac pacemakers, metallic implants or metal-containing tatoos
•history of allergic reactions
•known hypersensitivity to the study medication or to their adjuvants
•acute bleedings within the last two weeks, elevated risk of acute bleedings (ulcer, oesophageal varicosis, regular intake of coumarines) or subnormal haemoglobin value
•patients who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
•patients liable to orthostatic dysregulation, fainting, or blackouts
•lactation and pregnancy test positive or not performed
•repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)
•intake of grapefruit containing food or beverages within 7 days prior to administration

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the hepatic uptake of Primovist® after intravenous administration of 25 µmol/kg body weight in 32 healthy volunteers and in 60 patients with a liver disease in dependence on the OATP1B1-genotype;Secondary Objective: ;Primary end point(s): pharmacokinetic characteristics of Gd-EOB-DTPA;<br><br>signal intensity of liver, gallbladder and background noise<br> <br>calculation of the signal-to-noise ratio and of the percentage of enhancement of the signal intensities (percentage of average accumulation) after drug injection<br>