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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the pharmacokinetics (PK) of perampanel following oral suspension administration given as an adjunctive therapy in pediatric subjects from 2 to less than 12 years old with epilepsy
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E.2.2 | Secondary objectives of the trial |
To evaluate the short- and long-term safety and efficacy of perampanel oral suspension in pediatric subjects with epilepsy from 2 to less than 12 years of age
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, from 2 to less than 12 years of age at the time of consent/assent
2. Have a minimum weight of 10 kg (22 lb.)
3. Have had brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) prior to Visit 1 that ruled out a progressive cause of epilepsy
4. Have a diagnosis of epilepsy with any type of seizure according to the International League against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981). Diagnosis should have been established at least 6 months prior to Visit 1, by clinical history and an electroencephalogram (EEG) that is consistent with epilepsy; normal interracial EEGs will be allowed provided that the participant meets the other diagnosis criterion (ie, clinical history)
5. Have had one or more seizure(s) during the 4 weeks prior to Visit 1
6. Are currently being treated with stable doses of one to a maximum of 3 AEDs for at least 4 weeks prior to Visit 1 and throughout the study duration (Only one perampanel inducing AED [i.e. carbamazepine, oxcarbazepine, phenytoin] out of the maximum of 3 AEDs is allowed in at least one third of the participants in each age cohort and not to exceed one half of the population of each age cohort. The remaining participants should not be taking any inducer)
Note: this list is not exhaustive.
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E.4 | Principal exclusion criteria |
1. Have a history of status epilepticus that required hospitalization during the 6 months prior to Visit 1
2. Have current or a history of pseudo-seizures (psychogenic non-epileptic seizures [PNES]) from birth or within approximately 5 years prior to Visit 1
3. Have seizures due to treatable medical conditions, such as those arising due to metabolic disturbances, toxic exposure, or an active infection
4. Have epilepsy secondary to progressive cerebral disease or any other progressive neurodegenerative disease
5. Have had epilepsy surgery within 1 year prior to Visit 1
Note: this list is not exhaustive.
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E.5 End points |
E.5.1 | Primary end point(s) |
Only during Core Study:
1. Apparent clearance (cl/f) of perampanel; (2) steady-state average concentration (c av,ss) of perampanel
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
(1) and (2) From Day 8 up to Day 78 |
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E.5.2 | Secondary end point(s) |
For Core Study:
(1) Percent change from baseline in seizure frequency per 28 days in treatment phase; (2) 50% responder rate during the maintenance period-last observation carry forward (LOCF); (3) seizure-free rate during the maintenance period; (4) the clinical global impression of change at the end of treatment (EOT); (5) number of participants with treatment emergent non-serious adverse events (AEs) and treatment emergent serious adverse events (SAEs) as a measure of safety and tolerability of perampanel; and (6) palatability questionnaire assessment: how does this medicine taste; how does this medicine smell; based on its taste, smell, and how it felt in the mouth, how easy or difficult was it for you/your child to take this medicine every day; and would you/your child have preferred this medicine to have been flavored, eg, Fruity.
For Extension Phase:
(7) Percentage change from baseline in seizure frequency per 28 days during the overall treatment duration by 13-week intervals; (8) 50% responder rate during the overall treatment duration by 13-week intervals; (9) seizure-free rate during the overall treatment duration; and (10) the clinical global impression of change during the overall treatment duration by visit and at EOT.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1) Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 0 to Week 15; (2) Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 9 to 11; (3) Week 9 to Week 11; (4) Week 0 (Baseline), Week 11 or EOT; (5) For each participant, from the first treatment dose till 30 days after the last dose or up to Week 15 for Core Study and Week 56 for the Extension Phase; (6) Week 5 or at the time of early discontinuation; (7), (8), and (9) Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52; and (10) Week 0 (Baseline), Week 11, Week 28, Week 52 or EOT. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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As defined in the protocol. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 39 |