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 | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to study the potential effect of add-on fenfluramine in refractory Lennox Gastaut epilepsy. ( exploratory dose finding add-on trial).
Primary outcome:
Number of responders and seizure free patients (for all 4 major seizure types counted together) after each period (week 8, 12 and 16 and 20) and at each dosage (0,2 or 0,4 or 0,8 mg/kg/day) |
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E.2.2 | Secondary objectives of the trial |
Secondary:
Seizure frequency change per patient and per major seizure type (TCS, TS, AS, FS)
Adverse events
Sleep quality (scale to be discussed)
CGI (clinical global impression) at last visit , by patient/caregiver and treating physician
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Electro-clinical epilepsy syndrome compatible with Lennox Gastaut syndrome
Minimum requirements (based on ILAE epilepsydiagnosis.org)
- multiple seizure types including in any case tonic seizures
- EEG shows slow spike waves and abnormal background
- abnormal cognitive development
- MRI compatible with Lennox Gastaut epilepsy : no progressive disease
- Drug resistant :
- at least 4 documented seizures in the last 4 weeks before inclusion
(minimum 4 seizures in at least 2 separate weeks)
Seizure types eligible for inclusion are : generalized tonic-clonic seizures GTC , tonic seizures TS , atonic seizures AS or clearly recognizable focal seizures FS.
- on >= 2 AEDs (including VNS) during the 4 weeks before inclusion
(no changes in treatment before inclusion and during the trial)
- Age between 3 and 18 years
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E.4 | Principal exclusion criteria |
- Known clinical cardiovascular abnormalities (including valvular problems, shunts, pulmonary hypertension, exercise intolerance)
- Any cardiac ultrasound/ECG abnormalities at baseline
- Weight below percentile 3 for age at baseline
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of responders and seizure free patients (for all 4 major seizure types counted together) after each period (week 8, 12 and 16 and 20) and at each dosage (0,2 or 0,4 or 0,8 mg/kg/day) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
8, 12, 16 and 20 weeks after inclusion |
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E.5.2 | Secondary end point(s) |
Secondary:
Seizure frequency change per patient and per major seizure type (TCS, TS, AS, FS)
Adverse events
Sleep quality (scale to be discussed)
CGI (clinical global impression) at last visit , by patient/caregiver and treating physician
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
8, 12, 16 and 20 weeks after inclusion |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 | No |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |