Pharmacokinetic Study With an Oral Suspension of Perampanel as Adjunctive Therapy in Pediatric Subjects With Epilepsy

An Open-Label Study With an Extension Phase to Evaluate the Pharmacokinetics of Perampanel (E2007) Oral Suspension When Given as an Adjunctive Therapy in Subjects From 1 Month to Less Than 4 Years of Age With Epilepsy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02914314

Enrollment

Registered

2016-09-26

Start date

2017-02-20

Completion date

2023-04-25

Last updated

2024-03-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Epilepsy

Keywords

epilepsy, refractory partial seizures

Brief summary

The purpose of this study is to evaluate the pharmacokinetics (PK) of perampanel during the Maintenance Period of the Core Study following oral suspension administration given as an adjunctive therapy in pediatric participants from 1 month to less than 4 years of age with epilepsy.

Detailed description

This is a multicenter, open-label study comprised of pretreatment, treatment (core study), and extension phases that is designed to evaluate the PK of an oral suspension of perampanel (maximum dose must not exceed 12 milligrams per day \[mg /day\] for participants taking non-enzyme-inducing antiepileptic drug \[non-EIAED\] or 16 mg/day for participants taking EIAED) when given as an adjunctive therapy in participants ranging from 1 month to less than 4 years of age with epilepsy. The Pretreatment Phase will last up to 2 weeks, during which participants will be assessed for their eligibility to participate in the study. The Treatment Phase will consist of 3 periods: Titration (12 \[for participants taking non-EIAED\] to 16 weeks \[for participants taking EIAED\]), Maintenance (4 weeks), and Follow-Up (4 weeks; only for those participants who complete the Maintenance Period but do not continue into the Extension Phase and those participants who discontinue study participation). Extension Phase: The Extension Phase will consist of 2 periods: Maintenance (32 weeks \[for participants taking EIAED\]; 36 weeks \[for participants taking non-EIAED\]) and Follow-Up (4 weeks). The maximum total duration of treatment for each participant will be 52 weeks and the maximum total duration of the study for each participant will be 58 weeks (2 weeks Pretreatment+52 weeks of treatment+4 weeks Follow-up).

Interventions

DRUGperampanel

oral suspension.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

1 Months to 4 Years

Healthy volunteers

Inclusion criteria

* Male or female, from 1 month to less than 4 years of age (and of at least 36 weeks gestational age) at the time of consent * Have a minimum weight of 4 kilograms (kg) (8.8 pounds \[lb\]) * 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 2 weeks (≤6 months of age) or 4 weeks (\>6 months of age) before 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) * Have had brain imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) before Visit 1 that ruled out a progressive cause of epilepsy * Have had 1 or more seizure(s) before Visit 1 * Currently being treated with a stable dose (i.e., unchanged for at least 5 half-lives) of 1 to a maximum of 4 antiepileptic drugs (AEDs) (at least 6, but not more than 8, in the age group of 1 to less than 24 months, and up to 13 subjects in the age group of 2 to less than 4 years, will be taking 1 EIAEDs \[that is, carbamazepine (CBZ), oxcarbazepine (OXC), phenytoin (PHT), or eslicarbazepine (ESL)\] out of the maximum of 4 AEDs. The remaining participants cannot be taking any EIAEDs). * Have been on their current concomitant AED(s) with a stable dose for at least 2 weeks or 5 half-lives, whichever is longer, before Visit 1 * Must have discontinued all restricted medications (example, medications known to be inducers of cytochrome P450 3A) at least 2 weeks or 5 half-lives (whichever is longer) before Visit 1 * If entering the Extension Phase, must have completed the last visit of the Maintenance Period of the Core Study

Exclusion criteria

* Have a history of status epilepticus that required hospitalization during the 3 months before Visit 1 * Have seizures due to treatable medical conditions, such as those arising due to metabolic disturbances, toxic exposure, or an active infection * Have epilepsy secondary to progressive central nervous system (CNS) disease or any other progressive neurodegenerative disease, including tumors * Have had epilepsy surgery within 1 year of Visit 1 * Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1 * Used intermittent rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period considered one-time rescue) 2 or more times in the 2 weeks before Visit 1 * Current use of felbamate, or any evidence of ongoing hepatic or bone marrow dysfunction associated with prior felbamate treatment. (Prior use of felbamate must be discontinued at least 8 weeks before Visit 1.) * Current use of vigabatrin or any evidence of clinically significant vision abnormality associated with prior vigabatrin treatment. (Prior use of vigabatrin must be discontinued at least 2 weeks before Visit 1.) * Are on ketogenic diet regimen that has not been stable for at least 4 weeks before Visit 1 * Concomitant use of other drugs known to influence the CNS, (other than AEDs for epilepsy), where the dose has not been stabilized for at least 5 half-lives or 2 weeks, whichever is longer, before Visit 1 * Have any concomitant illnesses/co-morbidities that could severely affect the participant's safety or study conduct * Have 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 study conduct * Have clinically significant laboratory abnormalities or any clinically acute or chronic disease * Have 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) * Have clinical evidence of significant active hematological disease; white blood cell (WBC) count ≤2500/ microliter (μL) (2.50 x 10\^9/Liter \[L\]) or an absolute neutrophil count ≤1000/μL (1.00 x 10\^9/L) * Have conditions that may interfere with their participation in the study and/or with the PK of study drug * 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 * Have recently (within 30 days before Visit 1) been exposed to perampanel in a clinical study or by prescription, and/or previous discontinuation from perampanel treatment due to adverse events related to perampanel * Have a clinically significant ECG abnormality, including prolonged corrected QT interval (QTc) defined as \>450 milliseconds (msec) * Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions

Design outcomes

Primary

Measure	Time frame	Description
Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is the area under the curve during a dosing interval (tau, 24 hours) at steady state calculated using population pharmacokinetic (PK) model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated liquid chromatography mass spectrometry (LC MS/MS) analytical method.
Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized Cmax,ss was calculated as Cmax,ss/maintenance dose, where Cmax,ss is the maximum (peak) steady-state concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.
Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as the ratio of area under the curve (AUC)/tau, (tau = 24 hours for perampanel) using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.
Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized Cmin,ss was calculated as Cmin,ss/maintenance dose, where Cmin,ss is the minimum observed steady state plasma concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.
Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is the area under the curve during a dosing interval (tau, 24 hours) at steady state calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.
Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized Cmax,ss was calculated as Cmax,ss/maintenance dose, where Cmax,ss is the maximum (peak) steady-state concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.
Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as the ratio of area under the curve (AUC)/tau, (tau = 24 hours for perampanel) using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.
Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)	Dose normalized Cmin,ss was calculated as Cmin,ss/maintenance dose, where Cmin,ss is the minimum observed steady state plasma concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Secondary

Measure	Time frame	Description
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Albumin, globulin, protein were expressed as g/L. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	SBP and DBP were measured after the participant sitting or supine, for 5 minutes. SBP and DBP were expressed as millimeter of mercury (mmHg). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Pulse rate measured after the participant sitting or supine, for 5 minutes and was expressed in beats per minute (beats/min). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Respiratory rate was the number of breaths taken per minute, measured at rest. Respiratory rate was expressed as breaths per minute (breaths/min). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Body temperature was expressed as degree centigrade. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Height	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Height was expressed as centimeters. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Core Phase: From the first dose of study drug up to 4 weeks of follow up after the last dose in Core Phase (up to Week 24); Extension Phase: From end of Core Phase treatment up to 4 weeks of follow up after the last dose in Extension Phase (up to Week 56)	TEAE was an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline); or re-emerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment; or worsened in severity during treatment relative to the pretreatment state, when AE was continuous. SAE was any untoward medical occurrence that at any dose: Resulted in death; was life-threatening (meaning participant was at an immediate risk of death from AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect (in child of a participant who was exposed to the study drug).
Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Head circumference was expressed as centimeters. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core and Extension Phase: Mean Change From Baseline in ECG Parameters: Single Beat Heart Rate-corrected QT Interval (QTcB), QT Interval Corrected According to the Formula of Fridericia (QTcF), PR and QT Intervals, QRS Duration, and Aggregate RR Interval	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	QTc: time from beginning of QRS complex to end of T wave, corrected for heart rate. QT interval: time from ECG Q wave to end of T wave corresponding to electrical systole. QRS interval: time from ECG Q wave to end of S wave, corresponding to ventricle depolarization. PR interval: time between beginning of P wave and start of QRS interval, corresponding to end of atrial depolarization and onset of ventricular depolarization. RR interval: time elapsed between two successive R waves of QRS signal. Single beat QTcB, QTcF, PR and QT Interval, QRS duration and aggregate RR interval were expressed as millisecond (msec). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in ECG Parameter: ECG Ventricular Rate	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Ventricular rate is determined by dividing 60 by the mean RR interval of the ECG in seconds (mean time between QRS complexes) to get beats per minute. ECG ventricular rate was expressed as beats/min. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Thyrotropin was expressed as milli-international units per liter (mIU/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	IGF-1 was expressed as millimoles per liter\10\^-6 (mmol/L\10\^-6). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Free Thyroxine, and Free Triiodothyronine	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Free thyroxine, and free triiodothyronine were expressed as picomoles per liter (pmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Weight	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Weight was expressed as kilograms. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, and platelets were expressed as 10\^9 cells per liter (/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameter: Erythrocytes	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Erythrocytes was expressed as 10\^12 cells/L. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameter: Hemoglobin	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Hemoglobin was expressed as grams per liter (g/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Lactate Dehydrogenase	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase were expressed as units per liter (U/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Bilirubin was expressed as micromoles per liter (mcmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Calcium, chloride, cholesterol, glucose, phosphate, potassium, sodium, triglycerides, urea nitrogen were expressed as millimoles per liter (mmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)	Creatinine, direct bilirubin, urate were expressed as micromoles per liter (mcmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.

Countries

Latvia, United States

Participant flow

Recruitment details

Participants took part in the study at 8 investigative sites in the United States and Latvia from 20 February 2017 to 25 April 2023.

Pre-assignment details

A total of 26 participants were screened and enrolled, of which 5 were screen failure and 21 participants received the study treatment.

Participants by arm

Arm	Count
Cohort 1, Age >=1 to <=6 Months: Perampanel Participants of age range from \>=1 month to \<=6 months received perampanel 0.5 mg, oral suspension, before bedtime during Week 0 and then dose up titrated to a maximum of 12 mg/day (for participants who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for participants who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED participants and up to Week 16 for EIAED participants to identify each participant's optimum dose during Core Phase. Participants then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED participants) or 16 mg/day (for EIAED participants) as a maintenance dose for up to 4 weeks during Core Phase. All participants who completed Core Phase, entered Extension Phase, and continued their optimal perampanel dose in extension phase for up to Week 52. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED participants or up to 20 weeks for EIAED participants, and total treatment duration of Extension Phase was up to 36 weeks for non-EIAED participants and 32 weeks for EIAED participants.	4
Cohort 2, Age >6 to <=12 Months: Perampanel Participants of age range from \>6 to \<=12 months received perampanel 0.5 mg, oral suspension, before bedtime during Week 0 and then dose up titrated to a maximum of 12 mg/day (for participants who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for participants who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED participants and up to Week 16 for EIAED participants to identify each participant's optimum dose during Core Phase. Participants then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED participants) or 16 mg/day (for EIAED participants) as a maintenance dose for up to 4 weeks during Core Phase. All participants who completed Core Phase, entered Extension Phase, and continued their optimal perampanel dose in extension phase for up to Week 52. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED participants or up to 20 weeks for EIAED participants, and total treatment duration of Extension Phase was up to 36 weeks for non-EIAED participants and 32 weeks for EIAED participants.	5
Cohort 3, Age >12 to <24 Months: Perampanel Participants of age range from \>12 to \<24 months received perampanel 0.5 mg, oral suspension, before bedtime during Week 0 and then dose up titrated to a maximum of 12 mg/day (for participants who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for participants who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED participants and up to Week 16 for EIAED participants to identify each participant's optimum dose during Core Phase. Participants then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED participants) or 16 mg/day (for EIAED participants) as a maintenance dose for up to 4 weeks during Core Phase. All participants who completed Core Phase, entered Extension Phase, and continued their optimal perampanel dose in extension phase for up to Week 52. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED participants or up to 20 weeks for EIAED participants, and total treatment duration of Extension Phase was up to 36 weeks for non-EIAED participants and 32 weeks for EIAED participants.	9
Cohort 4, Age >=24 to <48 Months: Perampanel Participants of age range from \>=24 to \<48 months received perampanel 0.5 mg, oral suspension, before bedtime during Week 0 and then dose up titrated to a maximum of 12 mg/day (for participants who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for participants who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED participants and up to Week 16 for EIAED participants to identify each participant's optimum dose during Core Phase. Participants then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED participants) or 16 mg/day (for EIAED participants) as a maintenance dose for up to 4 weeks during Core Phase. All participants who completed Core Phase, entered Extension Phase, and continued their optimal perampanel dose in extension phase for up to Week 52. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED participants or up to 20 weeks for EIAED participants, and total treatment duration of Extension Phase was up to 36 weeks for non-EIAED participants and 32 weeks for EIAED participants.	3
Total	21

Withdrawals & dropouts

Period	Reason	FG002	FG003
Core Phase (Up to 20 Weeks)	Inadequate Therapeutic Effect	1	0
Core Phase (Up to 20 Weeks)	Lost to Follow-up	0	1
Core Phase (Up to 20 Weeks)	Withdrawal by Subject	0	1
Extension Phase (Up to 36 Weeks)	Participant choice	1	0
Extension Phase (Up to 36 Weeks)	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Cohort 1, Age >=1 to <=6 Months: Perampanel	Cohort 2, Age >6 to <=12 Months: Perampanel	Cohort 3, Age >12 to <24 Months: Perampanel	Cohort 4, Age >=24 to <48 Months: Perampanel	Total
Age, Continuous	5.5 months STANDARD_DEVIATION 0.58	10.2 months STANDARD_DEVIATION 0.84	18.8 months STANDARD_DEVIATION 3.73	31.3 months STANDARD_DEVIATION 4.16	16.0 months STANDARD_DEVIATION 8.76
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	0 Participants	2 Participants	1 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	5 Participants	7 Participants	2 Participants	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	2 Participants	0 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	5 Participants	7 Participants	2 Participants	17 Participants
Sex: Female, Male Female	2 Participants	3 Participants	7 Participants	1 Participants	13 Participants
Sex: Female, Male Male	2 Participants	2 Participants	2 Participants	2 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 5	0 / 9	0 / 3	0 / 4	0 / 5	0 / 8	0 / 1
other Total, other adverse events	2 / 4	5 / 5	9 / 9	2 / 3	2 / 4	5 / 5	8 / 8	1 / 1
serious Total, serious adverse events	2 / 4	1 / 5	2 / 9	1 / 3	3 / 4	1 / 5	3 / 8	0 / 1

Outcome results

Primary

Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants

Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is the area under the curve during a dosing interval (tau, 24 hours) at steady state calculated using population pharmacokinetic (PK) model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated liquid chromatography mass spectrometry (LC MS/MS) analytical method.

Time frame: Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)

Population: The PK Analysis Set was the group of participants with at least 1 PK assessment of perampanel during the Maintenance Period (Core Phase) with a documented dosing history. Here, overall number of participants analyzed signifies participants who were evaluable for this Outcome Measure (OM).

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	3840 nanogramhour per milliliter (ngh/mL)	Standard Deviation 2280
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	6110 nanogramhour per milliliter (ngh/mL)	Standard Deviation 1490
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	6030 nanogramhour per milliliter (ngh/mL)	Standard Deviation 1940
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	5810 nanogramhour per milliliter (ngh/mL)	—

Primary

Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants

Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is the area under the curve during a dosing interval (tau, 24 hours) at steady state calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	5220 ng*h/mL	Standard Deviation 3600
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	3300 ng*h/mL	Standard Deviation 1530
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	2510 ng*h/mL	—

Primary

Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants

Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as the ratio of area under the curve (AUC)/tau, (tau = 24 hours for perampanel) using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	160 ng/mL	Standard Deviation 95
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	255 ng/mL	Standard Deviation 62.2
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	251 ng/mL	Standard Deviation 80.8
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	242 ng/mL	—

Primary

Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants

Dose normalized Cmax,ss was calculated as Cmax,ss/maintenance dose, where Cmax,ss is the maximum (peak) steady-state concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	341 ng/mL	Standard Deviation 151
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	276 ng/mL	Standard Deviation 81.8
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	201 ng/mL	—

Primary

Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants

Dose normalized Cmin,ss was calculated as Cmin,ss/maintenance dose, where Cmin,ss is the minimum observed steady state plasma concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	172 ng/mL	Standard Deviation 145
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	90.5 ng/mL	Standard Deviation 53.4
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	69.2 ng/mL	—

Primary

Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants

Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as the ratio of area under the curve (AUC)/tau, (tau = 24 hours for perampanel) using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	217 ng/mL	Standard Deviation 150
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	137 ng/mL	Standard Deviation 63.8
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	105 ng/mL	—

Primary

Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants

Dose normalized Cmax,ss was calculated as Cmax,ss/maintenance dose, where Cmax,ss is the maximum (peak) steady-state concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	305 nanogram per milliliter (ng/mL)	Standard Deviation 73.1
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	388 nanogram per milliliter (ng/mL)	Standard Deviation 68.4
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	386 nanogram per milliliter (ng/mL)	Standard Deviation 103
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	341 nanogram per milliliter (ng/mL)	—

Primary

Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants

Dose normalized Cmin,ss was calculated as Cmin,ss/maintenance dose, where Cmin,ss is the minimum observed steady state plasma concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.

Time frame: Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)

Arm	Measure	Value (MEAN)	Dispersion
Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	114 ng/mL	Standard Deviation 96.4
Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	203 ng/mL	Standard Deviation 58.2
Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	199 ng/mL	Standard Deviation 71
Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	203 ng/mL	—

Secondary

Core and Extension Phase: Mean Change From Baseline in ECG Parameters: Single Beat Heart Rate-corrected QT Interval (QTcB), QT Interval Corrected According to the Formula of Fridericia (QTcF), PR and QT Intervals, QRS Duration, and Aggregate RR Interval

QTc: time from beginning of QRS complex to end of T wave, corrected for heart rate. QT interval: time from ECG Q wave to end of T wave corresponding to electrical systole. QRS interval: time from ECG Q wave to end of S wave, corresponding to ventricle depolarization. PR interval: time between beginning of P wave and start of QRS interval, corresponding to end of atrial depolarization and onset of ventricular depolarization. RR interval: time elapsed between two successive R waves of QRS signal. Single beat QTcB, QTcF, PR and QT Interval, QRS duration and aggregate RR interval were expressed as millisecond (msec). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.