Pharmacokinetics, Efficacy, and Safety of Perampanel Oral... | NCT01527006

Label	Type	Description	Intervention Names
perampanel	Experimental	Age Cohort 1 ( greater than or equal to 7 to less than 12 years of age at time of consent/assent) and age Cohort 2 ( greater than or equal to 2 to less than 7 years of age).	Drug: perampanel

Name	Type	Description	Arm Group Labels	Other Names
perampanel	Drug	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

Measure	Description	Time Frame
Apparent Clearance (CL/F) of Perampanel [Core Study]	CL/F was defined as the volume of plasma cleared of the drug per unit time. Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. The CL/F values were calculated for each visit and averaged to derive the total CL/F value per arm. Data was analyzed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/-standard deviation.	From Day 8 up to Day 78
Steady-state Average Concentration (C av,ss) of Perampanel [Core Study]	C av,ss was calculated as 'Dose (mg)/Dosing Interval (24 h)/(CL/F [L/h]) x 1000'. C av,ss during a dosing interval was dose-normalized to 0.12 mg/kg in participants aged ≥ 2 to less than 12 years (intended to correspond to 8 mg/70 kg in adults/adolescents). Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. C av,ss values were calculated for each visit and averaged to derive the total C av,ss value per arm. Data was analysed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/- standard deviation.	From Day 8 up to Day 78

Measure	Description	Time Frame
Percent Change From Baseline in Seizure Frequency Per 28 Days in Treatment Phase [Core Study]	Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The seizure frequency per 28 days was calculated the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. The data is presented as mean percent change +/- standard deviation.

Measure	Description	Time Frame
The Effect of Demographics on Population PK Parameters: AUC	This outcome was not assessed in the study.	11 weeks
The Effect of Demographics on Population PK Parameters: Cmax	This outcome was not assessed in the study.

Eligibility Module

Eligibility Criteria

Inclusion:

Have a minimum weight of 10 kg (22 lb)
Have had brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) prior to Visit 1 that ruled out a progressive cause of epilepsy
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)
Have had one or more seizure(s) during the 4 weeks prior to Visit 1
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)
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
Must have discontinued all restricted medications at least 2 weeks or five half-lives (whichever is longer) prior to Visit 1
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:

Have a history of status epilepticus that required hospitalization during the 6 months prior to Visit 1
Have current or a history of pseudo-seizures (psychogenic non-epileptic seizures [PNES]) from birth or within approximately 5 years prior to 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 cerebral disease or any other progressive neurodegenerative disease
Have had epilepsy surgery within 1 year prior to Visit 1
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
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
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
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
If ketogenic diet is used, participants must be on a stable regimen for at least 4 weeks prior to Visit 1
Have previously participated in a clinical trial involving perampanel

Name	Affiliation	Role
Michelle Gee	Eisai Limited	Study Director

PubMed Identifier	Type	Citation	Retractions
30739576	Derived	Renfroe JB, Mintz M, Davis R, Ferreira J, Dispoto S, Ferry J, Umetsu Y, Rege B, Majid O, Hussein Z, Laurenza A. Adjunctive Perampanel Oral Suspension in Pediatric Patients From >/=2 to <12 Years of Age With Epilepsy: Pharmacokinetics, Safety, Tolerability, and Efficacy. J Child Neurol. 2019 Apr;34(5):284-294. doi: 10.1177/0883073819827407. Epub 2019 Feb 10.

ID	Title	Description
FG000	Cohort ( ≥ 2 to < 7 Years of Age)	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

Percent Change From Baseline in Seizure Frequency Per 28 Days in Treatment Phase [Core Study]

Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The seizure frequency per 28 days was calculated the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. The data is presented as mean percent change +/- standard deviation.

The full analysis set, defined as participants who received study drug, had any seizure frequency data during the 2-week Pretreatment Phase plus the 4 weeks prior to the Pretreatment Phase (Visit 1), and during the Treatment Phase of the Core Study.

Posted

Median

Full Range

Percent change

Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 0 to Week 15

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants	OG00022 OG00128

Title

Denominators

Categories

Overall seizures

Title	Measurements
	OG000-43.6(-100 to 95.4) OG001-33.9(-100 to 1038.9)

Overall partial seizures

Title	Measurements
	OG000

Primary

Apparent Clearance (CL/F) of Perampanel [Core Study]

CL/F was defined as the volume of plasma cleared of the drug per unit time. Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. The CL/F values were calculated for each visit and averaged to derive the total CL/F value per arm. Data was analyzed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/-standard deviation.

The pharmacokinetic (PK) analysis set, defined as participants with at least 1 pharmacokinetic assessment of perampanel with a documented dosing history.

Posted

Mean

Standard Deviation

Liter per hour

From Day 8 up to Day 78

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

50% Responder Rate During the Maintenance Period-LOCF [Core Study]

Responder rate was defined as the proportion of participants with a 50% decrease in 28-day seizure frequency during the Maintenance Period compared to Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 Weeks Prior to Pretreatment Phase] for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. The data is presented as percent responders. LOCF = Last Observation Carried Forward.

Posted

Number

Percent responders

Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 9 to 11

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

Seizure-free Rate During the Maintenance Period [Core Study]

Seizure-free rate, defined as the percentage of participants who were seizure-free during the Maintenance Period. SG = Secondary Generalization.

Posted

Number

Percentage of participants

Week 9 to Week 11

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

The Clinical Global Impression of Change at the End of Treatment (EOT) [Core Study]

The Clinical Global Impression (CGI) evaluated perceived seizure frequency and severity, the occurrence of AEs, and overall functional status of the participant. The investigator performed the Clinical Global Impression of Severity for all participants at Baseline (Week 0). The evaluation used a 7-point scale where 1=normal, not at all ill and 7=extremely ill. The investigator performed the Clinical Global Impression of Change for all participants at the EOT (the duration after the day of first study drug dose up to 7 days after the last Core Phase drug dose, inclusive). The evaluation used a 7-point scale where 1=very much improved and 7=very much worse. This tool was used to assess the participant's status over the 4-week period prior to its completion compared to Baseline (Week 0).

The Full Analysis Set, defined as participants who received study drug, had any seizure frequency data during the 2-week Pretreatment Phase plus the 4 weeks prior to the Pretreatment Phase (Visit 1), and during the Treatment Phase of the Core Study.

Posted

Number

Participants

Week 0 (Baseline), Week 11 or EOT

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

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

An AE was defined as any untoward medical occurrence in a participant administered with the study drug. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening (ie, the participant was at immediate risk of death from the 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, or was as a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). In this study, treatment emergent AEs (defined as an AE (serious/non-serious) that started/increased in severity on/after the first dose of study drug up to 30 days after the final dose of study drug) were assessed. The details of the adverse events are presented in the safety section of the results.

The Safety Analysis Set included all subjects who took at least 1 dose of perampanel and had at least 1 postdose safety assessment during the Core Study and the Extension Phase.

Posted

Number

Participants

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

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

Palatability Questionnaire Assessment - How Does This Medicine Taste [Core Study]

The Palatability Questionnaire was answered directly by participants in Cohort ( ≥ 7 to ≤ 12 years) and indirectly by participants in Cohort ( ≥ 2 to ≤ 7 years) via their parents/caregivers. Participants selected their response from one of the five options (very good, good, not good-not bad, bad, very bad).

The Safety Analysis Set, defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

Posted

Number

Participants

Week 5 or at the time of early discontinuation

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

Palatability Questionnaire Assessment - How Does This Medicine Smell [Core Study]

The Safety Analysis Set, defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

Posted

Number

Participants

Week 5 or at the time of early discontinuation

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

Palatability Questionnaire Assessment - 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 [Core Study]

The Safety Analysis Set, defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

Posted

Number

Participants

Week 5 or at the time of early discontinuation

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Primary

Steady-state Average Concentration (C av,ss) of Perampanel [Core Study]

C av,ss was calculated as 'Dose (mg)/Dosing Interval (24 h)/(CL/F [L/h]) x 1000'. C av,ss during a dosing interval was dose-normalized to 0.12 mg/kg in participants aged ≥ 2 to less than 12 years (intended to correspond to 8 mg/70 kg in adults/adolescents). Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. C av,ss values were calculated for each visit and averaged to derive the total C av,ss value per arm. Data was analysed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/- standard deviation.

The PK analysis set, defined as participants with at least 1 pharmacokinetic assessment of perampanel with a documented dosing history.

Posted

Mean

Standard Deviation

ng/mL

From Day 8 up to Day 78

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Secondary

Palatability Questionnaire Assessment - Would You/Your Child Have Preferred This Medicine to Have Been Flavored, e.g. Fruity [Core Study]

The Safety Analysis Set, defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

Posted

Number

Participants

Week 5 or at the time of early discontinuation

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Other Pre-specified

The Effect of Demographics on Population PK Parameters: AUC

This outcome was not assessed in the study.

Posted

11 weeks

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants

Other Pre-specified

The Effect of Demographics on Population PK Parameters: Cmax

This outcome was not assessed in the study.

Posted

11 weeks

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants

Other Pre-specified

The Effect of Demographics on Population PK Parameters: Tmax

This outcome was not assessed in the study.

Posted

11 weeks

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants

Other Pre-specified

The Effect of the Most Common Concomitant AEDs on Population PK Parameters: AUC

This outcome was not assessed in the study.

Posted

11 weeks

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants

Other Pre-specified

The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Cmax

This outcome was not assessed in the study.

Posted

11 weeks

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants

Other Pre-specified

The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Tmax

This outcome was not assessed in the study.

Posted

11 weeks

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
OG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Units	Counts
Participants

Secondary

Percentage Change From Baseline in Seizure Frequency Per 28 Days During the Overall Treatment Duration by 13-week Intervals [Extension Phase]

The Full Analysis Set included all subjects who took at least 1 dose of perampanel during the Extension Phase, and had any seizure frequency data during the 2-week Pretreatment Phase plus the 4 weeks prior to Pretreatment Phase (Visit 1) of the Core Study and had any seizure frequency data during the Extension Phase.

Posted

Median

Full Range

Percent change

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

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

Secondary

50 % Responder Rate During the Overall Treatment Duration by 13-week Intervals [Extension Phase]

Responder rate was defined as the proportion of participants with a 50% decrease in 28-day seizure frequency during the overall treatment duration. The percentage of responders was assessed from Week 1 of perampanel treatment through successive 13-week intervals for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures with baseline as Pretreatment Phase (Visit 1) of 2 weeks plus 4 weeks Prior to Pretreatment Phase. The data is presented as percentage of responders.

Posted

Number

Percentage of responders

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

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

Secondary

Seizure-free Rate During the Overall Treatment Duration [Extension Phase]

Seizure-free rate, defined as the percentage of participants who were seizure-free during the Maintenance Period. The percentage of participants who were seizure free was assessed from Week 1 of perampanel treatment through successive 13-week intervals for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures with baseline as Pretreatment Phase (Visit 1) of 2 weeks plus 4 weeks Prior to Pretreatment Phase. The data is presented as the percentage of participants.

Posted

Number

Percentage of participants

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

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

Secondary

The Clinical Global Impression of Change During the Overall Treatment Duration by Visit and at EOT [Extension Phase]

The Clinical Global Impression (CGI) evaluated perceived seizure frequency and severity, the occurrence of AEs, and overall functional status of the participant. The investigator performed the Clinical Global Impression of Severity for all participants at Baseline (Week 0). The evaluation used a 7-point scale where 1=normal, not at all ill and 7=extremely ill. The investigator performed the Clinical Global Impression of Change for all participants at planned visit and at EOT (the duration after the day of first study drug dose up to 7 days after the Extension Phase drug dose, inclusive). The evaluation used a 7-point scale where 1=very much improved and 7=very much worse. This tool was used to assess the participant's status over the 4-week period prior to the planned/EOT visits compared to Baseline (Week 0).

Posted

Number

Participants

Week 0 (Baseline), Week 11, Week 28, Week 52 or EOT

ID	Title	Description
OG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Developmental Hip Dysplasia	Congenital, familial and genetic disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG0030 affected22 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Mastoiditis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Otitis Externa	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Otitis Media Acute	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Pneumonia	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Respiratory Syncytial Virus Bronchiolitis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Septic Shock	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Convulsion	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0022 affected19 at risk EG003
Abnormal Behaviour	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Mental Status Changes	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Hypotension	Vascular disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected28 at risk EG0020 affected19 at risk EG003
Cyanosis	Cardiac disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Cyclic Vomiting Syndrome	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Otitis Media	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Anticonvulsant Drug Level Increased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Foot Deformity	Musculoskeletal and connective tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Muscle Contracture	Musculoskeletal and connective tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Status Epilepticus	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0014 affected28 at risk EG0020 affected19 at risk EG0035 affected22 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0003 affected22 at risk EG0015 affected28 at risk EG0024 affected19 at risk EG003
Fatigue	General disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0018 affected28 at risk EG0021 affected19 at risk EG003
Gait Disturbance	General disorders	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0011 affected28 at risk EG0022 affected19 at risk EG003
Irritability	General disorders	MedDRA Version 16.1	Systematic Assessment	EG0003 affected22 at risk EG0015 affected28 at risk EG0023 affected19 at risk EG003
Pyrexia	General disorders	MedDRA Version 16.1	Systematic Assessment	EG0008 affected22 at risk EG0014 affected28 at risk EG0028 affected19 at risk EG003
Ear Infection	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0012 affected28 at risk EG0023 affected19 at risk EG003
Otitis Media	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0012 affected28 at risk EG0022 affected19 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0003 affected22 at risk EG0012 affected28 at risk EG0025 affected19 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0011 affected28 at risk EG0022 affected19 at risk EG003
Thyroxine Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0012 affected28 at risk EG0020 affected19 at risk EG003
Weight Increased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0013 affected28 at risk EG0021 affected19 at risk EG003
Decreased Appetite	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected28 at risk EG0022 affected19 at risk EG003
Increased Aappetite	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0013 affected28 at risk EG0021 affected19 at risk EG003
Ataxia	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0012 affected28 at risk EG0020 affected19 at risk EG003
Balance Disorder	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected28 at risk EG0021 affected19 at risk EG003
Dizziness	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0003 affected22 at risk EG0012 affected28 at risk EG0023 affected19 at risk EG003
Headache	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected28 at risk EG0022 affected19 at risk EG003
Lethargy	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected28 at risk EG0024 affected19 at risk EG003
Psychomotor Hyperactivity	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0012 affected28 at risk EG0020 affected19 at risk EG003
Somnolence	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0004 affected22 at risk EG0013 affected28 at risk EG0023 affected19 at risk EG003
Tremor	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0012 affected28 at risk EG0020 affected19 at risk EG003
Aggression	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0003 affected22 at risk EG0011 affected28 at risk EG0025 affected19 at risk EG003
Anxiety	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Insomnia	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected28 at risk EG0021 affected19 at risk EG003
Oppositional Defiant Disorder	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0011 affected28 at risk EG0022 affected19 at risk EG003
Tearfulness	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0003 affected22 at risk EG0011 affected28 at risk EG0024 affected19 at risk EG003
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0002 affected22 at risk EG0010 affected28 at risk EG0023 affected19 at risk EG003
Dermatitis Contact	Skin and subcutaneous tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected28 at risk EG0021 affected19 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Bradycardia	Cardiac disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Phimosis	Congenital, familial and genetic disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Ear Pain	Ear and labyrinth disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Conjunctivitis	Eye disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Eye Irritation	Eye disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Ocular Hyperaemia	Eye disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Photophobia	Eye disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Aphthous Stomatitis	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0023 affected19 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Gingival Recession	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Oral Mucosal Discolouration	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Autoimmune Disorder	Immune system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Atypical Pneumonia	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Bronchitis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Clostridium Difficile Infection	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Fungal Skin Infection	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Gastroenteritis Viral	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Influenza	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Lice Infestation	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0023 affected19 at risk EG003
Pharyngitis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Sinusitis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Tinea Capitis	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Viral Rash	Infections and infestations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Epiphyseal Fracture	Injury, poisoning and procedural complications	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Head Injury	Injury, poisoning and procedural complications	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Ligament Sprain	Injury, poisoning and procedural complications	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Blood Bicarbonate Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Blood Sodium Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Blood Triglycerides Increased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Blood Uric Acid Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Cardiac Murmur	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Cardiac Murmur Functional	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Globulins Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Heart Rate Increased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Tri-Iodothyronine Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Weight Decreased	Investigations	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Metabolic Acidosis	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Vitamin D Deficiency	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Posture Abnormal	Musculoskeletal and connective tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Cognitive Disorder	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Drooling	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Hypotonia	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Intention Tremor	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Sedation	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Speech Disorder	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Abnormal Behaviour	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Agitation	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Depressed Mood	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Disorientation	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Echolalia	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Emotional Disorder	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Hallucination	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Mood Altered	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Mood Swings	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Sleep Disorder	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Suicidal Ideation	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Enuresis	Renal and urinary disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Vulval Disorder	Reproductive system and breast disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Grunting	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0020 affected19 at risk EG003
Rhinitis Allergic	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Skin Disorder	Skin and subcutaneous tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0022 affected19 at risk EG003
Hypotension	Vascular disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected28 at risk EG0021 affected19 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Aurora	Colorado		United States

ID	Title	Description
BG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
BG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.	3	22	22	22
EG001	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.	5	28	25	28
EG002	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.	6	19	19	19
EG003	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase	During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.	7	22	22	22