E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Investigation in healthy volunteers and epilepsy patients |
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E.1.1.1 | Medical condition in easily understood language |
Investigation in healthy volunteers and epilepsy patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 |
• 20 patients with DRE without structural lesion on MRI (group 1)
• 25 patients with DRE with epileptogenic lesion on MRI (group 2)
• 25 seizure free patients (group 3)
• 10 patients with non-focal epilepsy (Exploratory group 4 )
• 20 healthy volunteers (10 per centre)
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of [11C]metoclopramide PET
To develop a kinetic model for quantification of [11C]metoclopramide PET data in brain
To assess radiolabeled metabolites of [11C]metoclopramide in plasma
To assess differences in [11C]metoclopramide metabolism between administration of a microdose (< 100 µg) and administration of a therapeutic dose (10 mg)
To retrospectively correlate the impact of ABCB1 SNPs on brain distribution of [11C]metoclopramide |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age: ≥18 years old
• Ability to comprehend the full nature and purpose of the study, including possible risks.
• Diagnosis:
o Group 1: drug resistant nonlesional focal epilepsy; suspected epileptogenic area will be delineated based on the results of phase 1 presurgical evaluation
o Group 2: drug resistant epilepsy patients with epileptogenic structural lesion (except seizures associated to tumors such as glioma II); suspected epileptogenic area will be delineated based on the results of phase 1 presurgical evaluation
o Group 3: Patients with focal epilepsy, who are seizure free for at least 1 year
o Group 4: Patients with multiregional seizure onset zones (lesional and nonlesional subjects may be included)
o Group 5: Healthy volunteers (serve as controls)
• 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 additional neurological or other diseases, which the investigator considers may affect the outcome of the study |
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E.4 | Principal exclusion criteria |
• Age:<18 years old
• Unwillingness to sign the informed consent
• Any abnormality found as part of the pre-treatment screening or in any of the performed laboratory tests that the investigator considers to interfere with the objectives of the study
• Intake of medication during two weeks before the start of the study, which the investigator considers may affect the validity of the study. Furthermore, intake of any drugs which may cause potential harm to the subject (e.g. anticoagulation for subjects undergoing arterial cannulation) is forbidden.
• Changes in medication within 2 weeks before the scan, which the investigator considers may affect the validity of the study
• Any disease or condition (e.g. pregnancy, breastfeeding, evolutive tumor) which the investigator considers may affect the subject’s safety or outcome of the study
• Exposure to radiation exceeding the allowed maximum foreseen by the current guidelines
• History of ethanol dependence and currently abstinent
• Inability to comprehend the full nature and purpose of the study
• Contraindication for PET or MR imaging e.g. claustrophobia, metallic endoprosthesis, non-MR safe implants |
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E.5 End points |
E.5.1 | Primary end point(s) |
kE,brain elimination slope for radioactivity washout from the brain |
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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) |
• kE,brain = elimination slope of radioactivity washout from the brain efflux clearance map
• 11C-metoclopramide pharmacokinetics in the blood over time
• 11C-metoclopramide parent fraction = 11C-metoclopramide metabolism in epilepsy patients (and the influence of co-medication and antiepileptic drug levels on it)
• K1, k2 and VT = compartmental modeling outcome parameters influx rate constant from plasma into brain (K1), efflux rate constant from brain into plasma (k2) and volume of distribution (VT) calculated from image derived input function (IDIF) (IDIF results will be validated with arterial blood sampling from a subgroup of patients)
• ABCB1 single nucleotide polymorphisms
• (fP) free fraction of 11C-metoclopramide fraction in plasma
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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) | 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 | No |
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 | 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 | No |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |