E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The effect of genetic polymorphisms on drug distribution will be investigated in healthy volunteers |
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E.1.1.1 | Medical condition in easily understood language |
No medical condition, genetic polymorphisms in healthy volunteers will be investigated |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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)
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E.5 End points |
E.5.1 | 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)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |