Pharmacokinetics, Efficacy, and Safety of Perampanel Oral Suspension on Seizure Frequency in Pediatric Subjects Maintained on One to Three Stable Antiepileptic Drugs

This is a multicenter, multiple ascending dose, open-label study (Core Study) with an
Extension Phase. The Core Study consisted of 2 phases, the Pretreatment Phase and the
Treatment Phase. The Pretreatment Phase lasted up to 2 weeks in duration, during which
participants were assessed for their eligibility to participate in the study. The Treatment
Phase consisted of 3 periods: Titration (7 weeks), Maintenance (4 weeks), and Follow-up (4
weeks; only for those participants not rolling over into the Extension Phase after
completing the Treatment Phase and for those participants who discontinued from the study).
All subjects who completed all scheduled visits up to and including the final visit of the
Treatment Phase (Core Study) were eligible to participate in the Extension Phase of the
study. The Extension Phase consisted of 2 periods: Maintenance (41 weeks) and Follow-up (4
weeks).

Inclusion:

1. Have a minimum weight of 10 kg (22 lb)

2. Have had brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI])
prior to Visit 1 that ruled out a progressive cause of epilepsy

3. 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 interictal EEGs will be allowed provided that the participant meets the other
diagnosis criterion (i.e. clinical history)

4. Have had one or more seizure(s) during the 4 weeks prior to Visit 1

5. Are currently being treated with stable doses of one to a maximum of three 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)

6. Have been on their current concomitant AED regimen for 2 months or more with a stable
dose for at least 4 weeks prior to Visit 1

7. Must have discontinued all restricted medications at least 2 weeks or five half-lives
(whichever is longer) prior to Visit 1

8. Females aged at least 8 years or of child-bearing potential must have a negative
serum beta-hCG at Visit 1 and a negative urine pregnancy test prior to titration at
Visit 2. Female participants of childbearing potential must agree for the duration of
the study and for a period of at least 60 days following administration of the last
dose of study drug to be abstinent or commit to the consistent and correct use of a
medically acceptable method of birth control (e.g., a double-barrier method [condom +
spermicide, condom + diaphragm with spermicide])

Exclusion:

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

6. Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit
1; however, those who have previously documented failed epilepsy surgery will be
allowed

7. Use of intermittent rescue benzodiazepines (i.e. 1-2 doses over a 24-hour period
considered one-time rescue) two or more times in a 30-day period prior to Visit 1

8. If felbamate is used as a concomitant AED, participants must be on felbamate for at
least 2 years, with a stable dose for 8 weeks prior to Visit 1. They must not have a
history of white blood cell (WBC) count below 2500/L (2.50 x 10^9/L), platelets below
100,000, liver function tests (LFTs) above 3 times the upper limit of normal (ULN),
or other indication of hepatic or bone marrow dysfunction while receiving felbamate.
If participants received felbamate in the past, it must have been discontinued 8
weeks prior to Visit 1

9. Have concomitant use of vigabatrin: participants who took vigabatrin in the past must
be off vigabatrin for approximately 5 months prior to Visit 1 and must have
documentation showing no evidence of a vigabatrin-associated clinically significant
abnormality in the visual perimetry test

10. If ketogenic diet is used, participants must be on a stable regimen for at least 4
weeks prior to Visit 1

11. Have previously participated in a clinical trial involving perampanel