Influence of the OATP1B1 and OATP1B3 Genotype on the Hepatic Uptake of Primovist®

This study has been completed.
Sponsor:
Information provided by:
University Medicine Greifswald
ClinicalTrials.gov Identifier:
NCT01420211
First received: August 16, 2011
Last updated: August 18, 2011
Last verified: August 2011
  Purpose

The objective of the study is to assess the hepatic uptake of Primovist® after intravenous administration of 25 µmol/kg body weight in 56 healthy volunteers and in 60 patients with a liver disease in dependence on the OATP1B1- and OATP1B3-genotype.


Condition Intervention Phase
Pharmacokinetics
MRI
Liver
Drug Transporter
Gd-EOB-DTPA
Drug: Primovist® 0,25 mmol/ml solution for injection
Device: MRI
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Influence of the OATP1B1 and OATP1B3 Genotype on the Hepatic Uptake of Primovist® in Healthy Volunteers and in Patients With Liver Disease

Resource links provided by NLM:


Further study details as provided by University Medicine Greifswald:

Primary Outcome Measures:
  • Pharmacokinetic characteristics [ Time Frame: before (serum blank) and 6, 11, 21, 31, 45, 65, 95, 125 min and 3, 4, 6, 8, 12, 24 and 48 h after drug administration ] [ Designated as safety issue: No ]
    AUC0-t is calculated by the trapezoidal formula. AUC0-t is assessed up to the last sampling time above the limit of quantitation and is extrapolated to infinity using standard techniques. Cmax and Tmax will be obtained directly from the measured concentration-time curves. t1/2 will be evaluated from the terminal slope by log-linear regression analysis.

  • signal intensity of liver [ Time Frame: before and 0.25, 1, 2, 3, 4, 5, 7, 8, 9, 10, 20, 30, 40, 50, 60, 90 and 120 min after drug administration ] [ Designated as safety issue: No ]
    Dynamic enhanced MR examination with 0.1ml/kg/KG (flow:2ml/s) Gd-EOB-DTPA and breath-hold gradient-echo T1-weighted VIBE images (Volumen interpolated breathhold examination) will be acquired on the 1.5T MRI (Siemens Symphony maestro class). Time of imaging can be seen on the time schedule. The SNR and the time to maximum enhancement will be calculated for each organ.


Secondary Outcome Measures:
  • signal intensity of gallbladder [ Time Frame: before and 0.25, 1, 2, 3, 4, 5, 7, 8, 9, 10, 20, 30, 40, 50, 60, 90 and 120 min after drug administration ] [ Designated as safety issue: No ]
    Dynamic enhanced MR examination with 0.1ml/kg/KG (flow:2ml/s) Gd-EOB-DTPA and breath-hold gradient-echo T1-weighted VIBE images (Volumen interpolated breathhold examination) will be acquired on the 1.5T MRI (Siemens Symphony maestro class). Time of imaging can be seen on the time schedule. The SNR and the time to maximum enhancement will be calculated for each organ.

  • signal intensity of background noise [ Time Frame: before and 0.25, 1, 2, 3, 4, 5, 7, 8, 9, 10, 20, 30, 40, 50, 60, 90 and 120 min after drug administration ] [ Designated as safety issue: No ]
    Dynamic enhanced MR examination with 0.1ml/kg/KG (flow:2ml/s) Gd-EOB-DTPA and breath-hold gradient-echo T1-weighted VIBE images (Volumen interpolated breathhold examination) will be acquired on the 1.5T MRI (Siemens Symphony maestro class). Time of imaging can be seen on the time schedule. The SNR and the time to maximum enhancement will be calculated for each organ.


Enrollment: 45
Study Start Date: October 2006
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primovist Drug: Primovist® 0,25 mmol/ml solution for injection
intravenous bolus injection of 25 µmol/kg (=0,1 ml/kg) body weight Primovist® and blood sampling before (serum blank) and 6, 11, 21, 31, 45, 65, 95, 125 min and 3, 4, 6, 8, 12, 24 and 48 h after drug administration
Device: MRI
lmaging of 20 slices (thickness: 3 mm; max. time of imaging 10 s) before and 0.25, 1, 2, 3, 4, 5, 7, 8, 9, 10, 20, 30, 40, 50, 60, 90 and 120 min after intravenous bolus injection of 25 µmol/kg (=0,1 ml/kg) body weight Primovist®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • age: 18 - 45 years
  • sex: male and female
  • ethnic origin: white
  • body weight: 19 to 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

Exclusion Criteria:

  • weight less than 45 kg
  • claustrophobia
  • cardiac pacemakers, metallic implants or metal-containing tatoos
  • history of allergic reactions, allergic deseases (e.g. asthma bronchiale)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420211

Locations
Germany
Department of Clinical Pharmacology at the University of Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany, 17487
Sponsors and Collaborators
University Medicine Greifswald
  More Information

No publications provided

Responsible Party: Prof. Dr. W. Siegmund, MD, Clinical Pharmacology at the University of Greifswald
ClinicalTrials.gov Identifier: NCT01420211     History of Changes
Other Study ID Numbers: Primovist - OATP1B1
Study First Received: August 16, 2011
Last Updated: August 18, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
European Union: European Medicines Agency

Keywords provided by University Medicine Greifswald:
pharmacokinetics
MRI
liver
drug transporter
Gd-EOB-DTPA

Additional relevant MeSH terms:
Gadolinium ethoxybenzyl DTPA
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014