The effect of genetic polymorphisms on drug distribution will be investigated in healthy volunteers
Conditions
Interventions
Product Name: Tariquidar
Pharmaceutical Form: Infusion
INN or Proposed INN: XR9576
CAS Number: 206873-63-4
Other descriptive name: TARIQUIDAR
Concentration unit: mg milligram(s)
Concentration type: ra
Sponsors
Medizinische Universität Wien
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Sex: female and male • Age: 18 - 65 years old • Normotensive after 5 min rest in a supine position • Normofrequent after 5 min rest in a supine position • No disease interferring with the study objectives (at investigators discretion) • Ability to comprehend the full nature and purpose of the study, including possible risks and side effects • Volunteers must sign the informed consent prior to inclusion in the study • No contraindication for MRI 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 65 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Any abnormality found as part of the pretreatment screening or in any of the laboratory tests performed that the investigators considers clinically relevant • Presence of any other ECG abnormality which the investigator considers clinically relevant • Intake of any medication, which the investigator considers may affect the validity of the study, due to interference with CYP3A4, Pgp or BCRP (Pgp inductors such as St. John’s wort, rifampicin or inhibitors such as esomeprazol, omeprazol, pantoprazol, lansoprazol, atrovastatin, itraconazol) or may cause potential harm to the subject (e.g. drug-drug interaction between tariquidar and loperamide or quinidine) • Contraindication to arterial cannulation (e.g. treatment with anticoagulants such as phenprocoumon or LMW heparines). • Participation in the evaluation of any drug within two weeks before the study day. • History of drug and alcohol abuse. • Blood donation within 1 month before the start of the study • Participation in clinical studies with exposure to radiation exceeding the allowed maximum foreseen by the current guidelines (http://ec.europa.eu/energy/nuclear/radioprotection/publication/doc/136_en.pdf). • Pregnancy or breastfeeding (female subjects)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: X To compare 11C-tariquidar and 11C-elacridar brain distribution before and during tariquidar infusion X To assess the influence of ABCB1 and ABCG2 SNPs on 11C-tariquidar and 11C-elacridar brain distribution before and during tariquidar infusion ;Secondary Objective: X To compare 11C-tariquidar and 11C-elacridar distribution to peripheral organs (e.g. liver, kidneys, heart, intestine, spleen) before and during tariquidar infusion X To assess the influence of ABCB1 and ABCG2 SNPs on 11C-tariquidar and 11C-elacridar distribution to peripheral organs before and during tariquidar infusion X? To confirm that the employed tariquidar dose achieves complete inhibition of Pgp at the BBB ;Primary end point(s): X Outcome parameters from pharmacokinetic modeling of 11C-tariquidar or 11C-elacridar brain PET data (total volume of distribution VT, influx rate constant from plasma into brain K1) before and during tariquidar infusion X Influence of ABCB1 and ABCG2 SNPs on 11C-tariquidar or 11C-elacridar brain PET outcome parameters (VT, K1) ;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): X Activity concentration (standardized uptake value SUV) of 11C-tariquidar or 11C-elacridar in peripheral organs (e.g. liver, kidneys, heart, intestine, spleen) before and during tariquidar infusion X Influence of ABCB1 and ABCG2 SNPs on activity concentration (SUV) of 11C-tariquidar or 11C-elacridar in peripheral organs before and during tariquidar infusion X Outcome parameters from pharmacokinetic modelling of (R)-11C-verapamil brain PET data (VT, K1, k2) before and during tariquidar infusion and tariquidar plasma PK;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Austria
Contacts
Public ContactKlinische Pharmakologie
Medizinische Universität Wien
Outcome results
None listed