Perampanel as Adjunctive Therapy in Pediatrics With Partial Onset Seizures or Primary Generalized Tonic Clonic Seizures

This is a multicenter, open-label, single-arm study in children (ages 4 to less than 12
years) with inadequately controlled POS or PGTC. The study will consist of a Core Study and
two Extension Phases (Extension A and Extension B). The Core Study will consist of the
following 2 phases: Pretreatment and Treatment Phase. The Pretreatment Phase, during which
participants will be assessed for eligibility, will consist of up to a 4-week ± 3 day
Screening/Baseline Period. The Treatment Phase will consist of 3 periods: up to an 11-week
Titration Period (dose titration on the basis of individual clinical response and
tolerability), up to a 12-week Maintenance Period (continuation of perampanel oral suspension
once daily at the dose level achieved at the end of the Titration Period), and up to a 4-week
Follow-up Period (only for those participants not rolling over into Extension A). Extension A
will consist of up to a 29-week Maintenance Period and up to a 4-week Follow-up Period. Visit
10 will be completed within 5 weeks ± 6 days of Visit 9. All participants who complete all
scheduled visits up to and including Visit 9 in the Treatment Phase will be eligible to
participate in Extension A of the study. During the Maintenance Period of Extension A, all
participants will continue with their optimal perampanel dose (i.e., dose level that they
completed on during the Core Study). Participants who do not continue in Extension A or those
who prematurely discontinue from the study will enter up to a 4-week Follow-up Period.
Participants in Japan and in countries where extended access programme cannot be implemented,
who have completed Extension A, may be eligible to participate in Extension B. Extension B
will consist of a Treatment Phase which will continue as long as clinically appropriate
according to the judgment of the investigator. Treatment of participants in Extension B will
be completed when the participant reaches 12 years of age or when perampanel is commercially
available in Japan for treatment of POS in pediatric participants (4 to <12 years of age).

Inclusion Criteria:

- Have a diagnosis of epilepsy with partial-onset seizures (POS) with or without
secondarily generalized seizures or primary generalized tonic-clonic (PGTC) seizures
according to the International League Against Epilepsy's (ILAE) Classification of
Epileptic Seizures (1981). A diagnosis should have been established at least 6 months
prior to Visit 1 by clinical history and an electroencephalogram (EEG) that is
consistent with the diagnosis; normal interictal EEGs will be allowed provided that
the participant meets the other diagnosis criterion (i.e., clinical history)

- Male or female participant, from age 4 to less than 12 years at the time of informed
consent/assent

- Have a minimum weight of 16 kilograms (kg) (35 pounds [lb])

- Have had a brain imaging (e.g., magnetic resonance imaging [MRI] scan or computed
tomography (CT)) before Visit 1 that ruled out a progressive cause of epilepsy

- During the 12 weeks ± 3 days (4 weeks ±3 days in Japan only) prior to Visit 2,
participants must have had equal or greater than 1 POS or 1 PGTC seizure. Only simple
POS with motor signs, complex POS, and complex POS with secondary generalization are
counted toward this inclusion for POS

- Are currently being treated with stable doses of 1 to a maximum of 3 approved
antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before to Visit
1; in the case where a new AED regimen has been initiated for a participant, the dose
must be stable for at least 8 weeks prior to Visit 1. Only 1 EIAED (defined as
carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of 3
AEDs is allowed (A vagal nerve stimulator [VNS] will be counted as one of the 3
allowed AEDs.)

Exclusion Criteria:

- Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
positive beta human chorionic gonadotropin (β-hCG) (or human chorionic gonadotropin
(hCG)) test with a minimum sensitivity of 25 International Units per liter (IU/L) or
equivalent units of β-hCG or hCG). A separate baseline assessment is required if a
negative screening pregnancy test was obtained more than 72 hours before the first
dose of study drug.

- Females of childbearing potential who:

- Had unprotected sexual intercourse within 30 days before study entry and who do not
agree to use a highly effective method of contraception (e.g., total abstinence, an
intrauterine device, a contraceptive implant, an oral contraceptive, or have a
vasectomized partner with confirmed azoospermia) throughout the entire study period or
for 28 days after study drug discontinuation. If a highly effective method is not
appropriate or acceptable for the participant, then the participant may use a
medically effective method (e.g., a double barrier method such as condom plus
diaphragm with spermicide).

- Are currently abstinent, and do not agree to use a double-barrier method (as described
above) or refrain from being sexually active during the study period or for 28 days
after study drug discontinuation.

- Are using hormonal contraceptives but are not on a stable dose of the same hormonal
contraceptive product for at least 4 weeks before dosing and who do not agree to use
the same contraceptive during the study or for 28 days after study drug
discontinuation.

- Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within
approximately 5 years before Visit 1.

- Have a history of status epilepticus that required hospitalization during the 6 months
before Visit 1.

- Have an unstable psychiatric diagnosis that may confound participants' ability to
participate in the study or that may prevent completion of the protocol-specified
tests (e.g., significant suicide risk, including suicidal behavior and ideation within
6 months before Visit 1, current psychotic disorder, acute mania).

- Any suicidal ideation with intent with or without a plan within 6 months before Visit
2 (i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the
Columbia Suicide Severity Rating Scale (C-SSRS)) in participants aged 6 and above.

- 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.

- Evidence of clinically significant disease (e.g., cardiac, respiratory,
gastrointestinal, renal disease) that in the opinion of the investigator(s) could
affect the participant's safety or interfere with the study assessments.

- Evidence of moderate or severe renal insufficiency as defined by estimated glomerular
filtration rates (eGFRs) of 31 to < 60 "milliliters per minute (mL/min)" and < 30
mL/min, respectively.

- Evidence of significant active hepatic disease. Stable elevation of liver enzymes,
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) due to concomitant
medication(s), will be allowed if they are less than 3 times the upper limit of normal
(ULN).

- Evidence of significant active hematological disease; white blood cell (WBC) count
equal or less than 2500/µL (2.50 1E+09/liter [L]) or an absolute neutrophil count
equal or less than 1000/µL (1.00 1E+09/L).

- Clinically significant electrocardiogram (ECG) abnormality, including prolonged
corrected QT interval (QTc) defined as greater than 450 milliseconds (msec).

- Have a progressive central nervous system (CNS) disease, including degenerative CNS
diseases and progressive tumors.

- Multiple drug allergies or a severe drug reaction to an AED(s), including
dermatological (e.g., Stevens Johnson syndrome), hematological, or organ toxicity
reactions.

- Concomitant use of felbamate as an AED for less than 2 years or where the dose has not
been stable for at least 8 weeks before Visit 1. Participants must not have a history
of WBC count equal to or less than 2500/µL, platelets below 100,000, liver function
tests (LFTs) above 3 times the 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 before Visit 1 to be eligible for study
participation.

- Concomitant use of vigabatrin: participants who took vigabatrin in the past must be
off vigabatrin for at least 5 months before Visit 1 and with documentation showing no
evidence of a vigabatrin-associated clinically significant abnormality in a visual
perimetry test.

- Concomitant use of cannabinoids

- Used benzodiazepines for epilepsy during which the dose has not been stable for
greater than 4 weeks prior to Visit 1. Benzodiazepines use as rescue medication for
seizure control is allowed; however, intermittent use of benzodiazepines for any other
indication (eg, anxiety/sleep disorders) is prohibited.

- A VNS implanted less than 5 months before Visit 1 or changes in parameter less than 4
weeks before Visit 1 (or thereafter during the study)

- On a ketogenic diet for which the diet is not a stable regimen for at least 4 weeks
before Visit 1.

- History of or a concomitant medical condition that in the opinion of the
investigator(s) would preclude the participant's participation in a clinical study or
compromise the participant's ability to safely complete the study.

- Have previously been exposed to perampanel in a clinical trial or by prescription for
more than 2 months or discontinued for Adverse Events (AEs).

- Have participated in a study involving administration of an investigational drug or
device within 4 weeks before Visit 1, or within approximately 5 half-lives of the
previous investigational compound, whichever is longer.

- Participants with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption.