E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043209 |
E.1.2 | Term | Temporal lobe epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
To assess Pgp function at the BBB before and after epilepsy surgery To assess epilepsy surgery outcome
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E.2.2 | Secondary objectives of the trial |
To measure regional cerebral blood flow To assess the feasibility of PET/MRI based generation of an image derived input function and metabolite analysis from venous samples as an alternative to arterial blood sampling in TLE patients To assess immunohistochemistry on resected brain tissue To assess the influence of ABCB1 single nucleotide polymorphisms on (R)-11C-verapamil distribution to the brain.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed informed consent • Age: ≥18 years old • Physical examination and laboratory analysis: no presence of clinically relevant abnormal findings or values which the investigator considers may interfere with the objectives of the present study • No diseases, which the investigator considers may affect the outcome of the study • Lifetime diagnosis therapy refractory TLE, preferably hippocampal sclerosis • Ability to comprehend the full nature and purpose of the study, including possible risks and side effects Group 1 only: Eligible and scheduled for epilepsy surgery Group 2a only: History of epilepsy surgery, seizure free and no AED medication since at least one year Group 2b only: History of epilepsy surgery, seizure free, regularly on AED medication
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E.4 | Principal exclusion criteria |
• Unwillingness to sign the informed consent • Age:<18 years old • Any abnormality found as part of the pre-treatment screening or in any of the laboratory tests performed that the investigator considers to interfere with the objectives of the present study • Intake of medication during two weeks before the start of the study, which the investigator considers may affect the validity of the study, due to interference with CYP3A4 or Pgp (Pgp inductors such as St. John’s wort, rifampicin or inhibitors such as esomeprazole, omeprazole, pantoprazole, lansoprazole, atrovastatin, itraconazole), or which may cause potential harm to the subject (e.g. anticoagulation) • Changes in the medication within 2 weeks before the PET scan, which the investigator considers may affect the validity of the study • Any disease or medical condition (e.g. pregnancy) which the investigator considers may affect the outcome of the study • Participation in the evaluation of any drug within four weeks before the start of the study or participation in clinical studies with exposure to radiation exceeding the allowed maximum foreseen by the current guidelines (http://ec.europa.eu/energy) • Inability to comprehend the full nature and purpose of the study • Contraindication for MRI imaging e.g. claustrophobia, metallic endoprosthesis, stent implantation in the last months • History of alcohol abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
Regional (R)-11C-verapamil influx rate constant (K1) across the BBB expressed as ml/min/cm3. Epilepsy surgery outcome according to Wieser’s classification.
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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) |
MRI based calculation of cerebral blood flow (millilitres per minute) PET based image derived input function (kBq/SUV) Measurement of (R)-11C-verapamil metabolites in arterial and venous blood Determine ABCB1 single nucleotide polymorphisms (SNPs, 3435C>T, 2677G>T, 1236C>T) and the effects of genetic polymorphisms on (R)-11C-verapamil brain distribution Immunohistochemistry (resected brain tissue): % of Pgp positive labelled area Behavioral assessments including quality of life and seizure scores
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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 | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | Yes |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |