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

NCT01420211 | Completed Phase 1

• 1 other identifier: Primovist - OATP1B1
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics; MRI; Liver; Drug Transporter; Gd-EOB-DTPA

Keywords

pharmacokinetics; MRI; liver; drug transporter; Gd-EOB-DTPA

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic characteristics

  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.

  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

• signal intensity of liver

  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.

  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

Secondary Outcomes (2)

• signal intensity of gallbladder

  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

• signal intensity of background noise

  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

Study Arms (1)

Primovist

EXPERIMENTAL

Drug: Primovist® 0,25 mmol/ml solution for injection; Device: MRI

Interventions

Primovist® 0,25 mmol/ml solution for injection DRUG

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

Primovist

MRI DEVICE

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®

Primovist

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medicine Greifswald: lead

Study Sites (1)

Department of Clinical Pharmacology at the University of Greifswald

Greifswald, Mecklenburg-Vorpommern, 17487, Germany

Location

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 16, 2011
• First Posted: August 19, 2011
• Study Start: October 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 19, 2011

Record last verified: 2011-08

Locations

DE (1)