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Clinical Trial Results:
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

Summary
EudraCT number	2013-005391-17
Trial protocol	LV
Global end of trial date	25 Apr 2023

Results information
Results version number	v2(current)
This version publication date	11 Feb 2024
First version publication date	08 Nov 2023
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

E2007-G000-238

ISRCTN number

US NCT number

NCT02914314

WHO universal trial number (UTN)

Sponsor organisation name

Eisai Ltd.

Sponsor organisation address

European Knowledge Centre, Mosquito Way, Hatfield, Hertfordshire, United Kingdom, AL10 9SN

Public contact

EMEA Medical Information, Eisai Ltd., +44 (0)208 600 1400, EUMedInfo@eisai.net

Scientific contact

EMEA Medical Information, Eisai Ltd., +44 (0)208 600 1400, EUMedInfo@eisai.net

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000467-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

25 Apr 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 Apr 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was 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 subjects from 1 month to less than 4 years of age with epilepsy.

Protection of trial subjects

This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Feb 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Latvia: 7

Country: Number of subjects enrolled

United States: 14

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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

Screening details

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

Period 1 title

Core Phase (Up to 20 weeks)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Arm description

Subjects of age range from greater than or equal to (>=) 1 month to less than or equal to (<=) 6 months received perampanel 0.5 milligrams (mg), oral suspension, before bedtime during Week 0 and then dose up titrated to a maximum of 12 milligram per day (mg/day) (for subjects who are not taking any EIAED]), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED subjects) or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 16 weeks (for non-EIAED subjects) and 20 weeks (for EIAED subjects) in Core Phase.

Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Arm description

Subjects of age range from greater than (>) 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED subjects) or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 16 weeks (for non-EIAED subjects) and 20 weeks (for EIAED subjects) in Core Phase.

Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Arm description

Subjects of age range from >12 to less than (<) 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED subjects) or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 16 weeks (for non-EIAED subjects) and 20 weeks (for EIAED subjects) in Core Phase.

Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Arm description

Subjects 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose up to 12 mg/day (for non-EIAED subjects) or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 16 weeks (for non-EIAED subjects) and 20 weeks (for EIAED subjects) in Core Phase.

Number of subjects in period 1	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Started	4	5	9	3
Subjects who did not take EIAED	4	3 ^[1]	5 ^[2]	1
Subjects who took EIAED	0 ^[3]	2 ^[4]	4 ^[5]	2
Completed	4	5	8	1
Not completed	0	0	1	2
Inadequate Therapeutic Effect	-	-	1	-
Consent withdrawn by subject	-	-	-	1
Lost to follow-up	-	-	-	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who did not take EIAED.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who did not take EIAED.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who took EIAED.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who took EIAED.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who took EIAED.

Period 2 title

Extension Phase (Up to 36 weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Arm description

Subjects of age range from >=1 month to <=6 months who completed the Core Phase continued their optimal perampanel oral suspension, at the dose level achieved at the end of the Treatment Phase. The maximum total daily allowed dose for a non-EIAED subject was 12 mg and 16 mg for EIAED subjects. The total treatment duration of Extension Phase was up to 36 weeks for non-EIAED subjects and 32 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 36 weeks (for non-EIAED subjects) and 32 weeks (for EIAED subjects) after core phase.

Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Arm description

Subjects of age range from >6 to <=12 months who completed the Core Phase continued their optimal perampanel oral suspension, at the dose level achieved at the end of the Treatment Phase. The maximum total daily allowed dose for a non-EIAED subject was 12 mg and 16 mg for EIAED subjects. The total treatment duration of Extension Phase was up to 36 weeks for non-EIAED subjects and 32 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 36 weeks (for non-EIAED subjects) and 32 weeks (for EIAED subjects) after core phase.

Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Arm description

Subjects of age range from >12 to <24 months who completed the Core Phase continued their optimal perampanel oral suspension, at the dose level achieved at the end of the Treatment Phase. The maximum total daily allowed dose for a non-EIAED subject was 12 mg and 16 mg for EIAED subjects. The total treatment duration of Extension Phase was up to 36 weeks for non-EIAED subjects and 32 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 36 weeks (for non-EIAED subjects) and 32 weeks (for EIAED subjects) after core phase.

Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Arm description

Subjects of age range from >=24 to <48 months who completed the Core Phase continued their optimal perampanel oral suspension, at the dose level achieved at the end of the Treatment Phase. The maximum total daily allowed dose for a non-EIAED subject was 12 mg and 16 mg for EIAED subjects. The total treatment duration of Extension Phase was up to 36 weeks for non-EIAED subjects and 32 weeks for EIAED subjects.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received perampanel oral suspension, once daily for up to 36 weeks (for non-EIAED subjects) and 32 weeks (for EIAED subjects) after core phase.

Number of subjects in period 2	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Started	4	5	8	1
Completed	4	5	6	1
Not completed	0	0	2	0
Consent withdrawn by subject	-	-	1	-
Subject choice	-	-	1	-

Baseline characteristics

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Reporting group title

Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Reporting group description

Reporting group values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Total
Number of subjects	4	5	9	3	21
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	4	5	9	0	18
Children (2-11 years)	0	0	0	3	3
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0
From 65-84 years	0	0	0	0	0
85 years and over	0	0	0	0	0
Age Continuous
Units: months
arithmetic mean (standard deviation)	5.5 ( 0.58 )	10.2 ( 0.84 )	18.8 ( 3.73 )	31.3 ( 4.16 )	-
Sex: Female, Male
Units: subjects
Female	2	3	7	1	13
Male	2	2	2	2	8
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0
Asian	1	0	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	0	2	0	2
White	3	5	7	2	17
More than one race	0	0	0	1	1
Unknown or Not Reported	0	0	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	0	2	1	4
Not Hispanic or Latino	3	5	7	2	17
Unknown or Not Reported	0	0	0	0	0

End points

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Reporting group title

Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Reporting group description

Subject analysis set title

Core Phase,Cohort 1,Age>=1 to<=6 Months:Perampanel(Non-EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects of age range from >=1 to <=6 months received perampanel 0.5 mg, oral suspension, before bedtime during Week 0 and then dose up titrated to 12 mg/day (for subjects who are not taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects.

Subject analysis set title

Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(Non-EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects 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 12 mg/day (for subjects who are not taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects.

Subject analysis set title

Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(Non-EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects 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 12 mg/day (for subjects who are not taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects.

Subject analysis set title

Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(Non-EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects 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 12 mg/day (for subjects who are not taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects.

Subject analysis set title

Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects 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 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 20 weeks for EIAED subjects.

Subject analysis set title

Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects 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 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 20 weeks for EIAED subjects.

Subject analysis set title

Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(EIAED)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects 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 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 20 weeks for EIAED subjects.

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

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End point title

Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Subjects ^[1]

End point description

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. PK Analysis Set was group of subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. Here, "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject.

End point type

Primary

End point timeframe

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)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 1,Age>=1 to<=6 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(Non-EIAED)
Number of subjects analysed	4	3	4	1
Units: nanogram per milliliter (ng/mL)
arithmetic mean (standard deviation)	305 ( 73.1 )	388 ( 68.4 )	386 ( 103 )	341 ( 99999 )

No statistical analyses for this end point

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 Subjects

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End point title

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 Subjects ^[2]

End point description

Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is area under 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 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. PK Analysis Set was group of subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. Here, "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject.

End point type

Primary

End point timeframe

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)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 1,Age>=1 to<=6 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(Non-EIAED)
Number of subjects analysed	4	3	4	1
Units: nanogramhour per milliliter (ngh/mL)
arithmetic mean (standard deviation)	3840 ( 2280 )	6110 ( 1490 )	6030 ( 1940 )	5810 ( 99999 )

No statistical analyses for this end point

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

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End point title

Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Subjects ^[3]

End point description

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. PK Analysis Set was group of subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. Here, "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject.

End point type

Primary

End point timeframe

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)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 1,Age>=1 to<=6 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(Non-EIAED)
Number of subjects analysed	4	3	4	1
Units: ng/mL
arithmetic mean (standard deviation)	160 ( 95 )	255 ( 62.2 )	251 ( 80.8 )	242 ( 99999 )

No statistical analyses for this end point

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

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End point title

Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Subjects ^[4]

End point description

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. PK Analysis Set was group of subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. Here, "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject.

End point type

Primary

End point timeframe

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)

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 1,Age>=1 to<=6 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(Non-EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(Non-EIAED)
Number of subjects analysed	4	3	4	1
Units: ng/mL
arithmetic mean (standard deviation)	114 ( 96.4 )	203 ( 58.2 )	199 ( 71 )	203 ( 99999 )

No statistical analyses for this end point

Primary: Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

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End point title

Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects ^[5]

End point description

Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is area under curve during 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. PK Analysis Set: subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject. No EIAED subject for Cohort 1, hence that arm not reported.

End point type

Primary

End point timeframe

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)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(EIAED)
Number of subjects analysed	2	3	1
Units: ng*h/mL
arithmetic mean (standard deviation)	5220 ( 3600 )	3300 ( 1530 )	2510 ( 99999 )

No statistical analyses for this end point

Primary: Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

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End point title

Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects ^[6]

End point description

Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as ratio of area under 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. PK Analysis Set: subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject. No EIAED subject for Cohort 1, hence that arm not reported.

End point type

Primary

End point timeframe

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)

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(EIAED)
Number of subjects analysed	2	3	1
Units: ng/mL
arithmetic mean (standard deviation)	217 ( 150 )	137 ( 63.8 )	105 ( 99999 )

No statistical analyses for this end point

Primary: Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

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End point title

Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects ^[7]

End point description

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. PK Analysis Set was group of subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. Here, "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject. No EIAED subject for Cohort 1, hence that arm not reported.

End point type

Primary

End point timeframe

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)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(EIAED)
Number of subjects analysed	2	3	1
Units: ng/mL
arithmetic mean (standard deviation)	341 ( 151 )	276 ( 81.8 )	201 ( 99999 )

No statistical analyses for this end point

Primary: Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

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End point title

Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects ^[8]

End point description

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. PK Analysis Set was group of subjects with at least 1 PK assessment of perampanel during Maintenance Period (Core Phase) with documented dosing history. Here, "Number of Subjects Analyzed" = subjects evaluable for this endpoint and "99999"=data could not be calculated for 1 subject. No EIAED subject for Cohort 1, hence that arm not reported.

End point type

Primary

End point timeframe

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)

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not planned for this endpoint.

End point values	Core Phase,Cohort 2,Age>6 to<=12 Months:Perampanel(EIAED)	Core Phase,Cohort 3,Age>12 to<24 Months:Perampanel(EIAED)	Core Phase,Cohort 4,Age>=24 to<48 Months:Perampanel(EIAED)
Number of subjects analysed	2	3	1
Units: ng/mL
arithmetic mean (standard deviation)	172 ( 145 )	90.5 ( 53.4 )	69.2 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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End point title

Core Phase and Extension Phase: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

End point description

TEAE: 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: any untoward medical occurrence that at any dose: Resulted in death; was life-threatening (meaning subject 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 subject who was exposed to the study drug). Safety Analysis Set (SAS) was group of subjects who received at least 1 dose of the study drug and had at least 1 post-dose safety assessment.

End point type

Secondary

End point timeframe

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)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	8	3	1
Units: subjects
Number of Subjects With TEAEs	3	4	5	5	9	8	3	1
Number of Subjects With SAEs	2	3	1	1	2	3	1	0

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets

End point description

Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, and platelets were expressed as 10^9 cells/liter. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "n" signifies subjects who were evaluable for specified categories. Here, "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	3	5	5	7	6	2	1
Units: 10^9 cells per liter (/L)
arithmetic mean (standard deviation)
Change in Basophils (n= 3, 5, 7, 2, 3, 5, 6, 1)	0.03 ( 0.058 )	0.03 ( 0.058 )	-0.02 ( 0.110 )	0.04 ( 0.219 )	-0.06 ( 0.151 )	-0.05 ( 0.122 )	0.00 ( 0.000 )	0.00 ( 99999 )
Change in Eosinophils (n= 3, 5, 7, 2, 3, 5, 6, 1)	-0.03 ( 0.115 )	0.10 ( 0.100 )	-0.00 ( 0.100 )	0.02 ( 0.148 )	-0.04 ( 0.513 )	-0.05 ( 0.399 )	-0.15 ( 0.212 )	0.00 ( 99999 )
Change in Leukocytes (n= 3, 5, 7, 2, 3, 5, 6, 1)	1.73 ( 2.316 )	2.43 ( 1.601 )	1.26 ( 5.855 )	-0.76 ( 4.558 )	1.10 ( 3.062 )	-1.08 ( 4.712 )	2.82 ( 6.187 )	-1.45 ( 99999 )
Change in Lymphocytes (n= 3, 5, 7, 2, 3, 5, 6, 1)	1.00 ( 1.500 )	0.53 ( 0.757 )	0.62 ( 2.448 )	-0.24 ( 1.627 )	0.54 ( 2.099 )	-1.38 ( 2.555 )	-1.73 ( 0.813 )	-1.75 ( 99999 )
Change in Monocytes (n= 3, 5, 7, 2, 3, 5, 6, 1)	-0.13 ( 0.153 )	0.10 ( 0.100 )	0.10 ( 0.308 )	-0.10 ( 0.292 )	0.10 ( 0.606 )	-0.02 ( 0.325 )	0.33 ( 0.672 )	0.25 ( 99999 )
Change in Neutrophils (n= 3, 5, 7, 2, 3, 5, 6, 1)	0.90 ( 0.781 )	1.70 ( 0.954 )	0.60 ( 3.820 )	-0.46 ( 2.518 )	0.51 ( 1.975 )	0.38 ( 3.019 )	4.35 ( 6.435 )	0.10 ( 99999 )
Change in Platelets (n= 2, 5, 4, 2, 2, 5, 5, 1)	-44.00 ( 108.894 )	7.50 ( 98.288 )	-63.80 ( 192.587 )	-32.00 ( 280.306 )	63.00 ( 167.127 )	23.80 ( 147.041 )	-22.50 ( 57.276 )	-85.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Erythrocytes

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Erythrocytes

End point description

Erythrocytes was expressed as 10^12 cells/L. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	3	5	5	7	6	2	1
Units: 10^12 cells/L
arithmetic mean (standard deviation)	0.44 ( 0.576 )	0.27 ( 0.329 )	0.16 ( 0.501 )	0.39 ( 0.919 )	0.10 ( 0.155 )	-0.14 ( 0.396 )	-0.10 ( 0.283 )	-0.03 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Hemoglobin

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Hemoglobin

End point description

Hemoglobin was expressed as grams per liter (g/L). Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	3	5	5	7	6	2	1
Units: g/L
arithmetic mean (standard deviation)	14.00 ( 18.000 )	10.00 ( 8.888 )	5.20 ( 8.899 )	12.80 ( 20.945 )	3.14 ( 3.237 )	-1.33 ( 13.808 )	-0.25 ( 3.889 )	-6.50 ( 99999 )

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	7	7	2	1
Units: U/L
arithmetic mean (standard deviation)
Change in Alanine Aminotransferase	-2.25 ( 7.932 )	36.50 ( 90.820 )	-16.00 ( 27.803 )	-16.00 ( 27.313 )	-13.71 ( 33.265 )	-11.43 ( 37.228 )	6.00 ( 15.556 )	-4.00 ( 99999 )
Change in Alkaline Phosphatase	43.50 ( 115.610 )	-12.75 ( 97.072 )	266.00 ( 652.320 )	-32.40 ( 147.179 )	23.86 ( 21.162 )	-77.29 ( 205.368 )	-46.50 ( 53.033 )	-58.00 ( 99999 )
Change in Aspartate Aminotransferase	-2.00 ( 2.449 )	21.00 ( 58.980 )	-12.20 ( 21.993 )	-13.20 ( 22.477 )	-6.57 ( 16.009 )	-8.43 ( 19.569 )	0.50 ( 3.536 )	1.00 ( 99999 )
Change in Gamma Glutamyl Transferase	12.50 ( 87.577 )	50.00 ( 320.278 )	-3.00 ( 3.536 )	-5.40 ( 4.336 )	-15.71 ( 31.653 )	-23.71 ( 48.801 )	5.00 ( 5.657 )	-1.00 ( 99999 )
Change in Lactate Dehydrogenase	-6.00 ( 50.721 )	1.00 ( 68.775 )	-32.60 ( 54.574 )	-44.60 ( 49.863 )	-14.43 ( 28.425 )	-17.29 ( 67.037 )	51.50 ( 132.229 )	-39.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin

End point description

Bilirubin was expressed as micromoles per liter (mcmol/L). Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	7	7	2	1
Units: mcmol/L
arithmetic mean (standard deviation)	-0.30 ( 0.600 )	-0.10 ( 0.200 )	0.64 ( 2.057 )	1.24 ( 2.414 )	-0.46 ( 1.555 )	-0.57 ( 1.093 )	0.70 ( 0.990 )	0.90 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen

End point description

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. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "n" signifies subjects who were evaluable for specified categories. Here, "99999" signifies data could not be calculated due insufficient or no subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	7	7	2	1
Units: mmol/L
arithmetic mean (standard deviation)
Change in Calcium (n=4,5,7,2,4,5,7,1)	-0.08 ( 0.147 )	-0.05 ( 0.123 )	0.02 ( 0.095 )	0.05 ( 0.139 )	-0.00 ( 0.098 )	-0.02 ( 0.103 )	-0.01 ( 0.014 )	-0.04 ( 99999 )
Change in Chloride (n=4,5,7,2,4,5,7,1)	-0.25 ( 2.500 )	0.00 ( 2.160 )	-0.80 ( 1.304 )	-2.60 ( 3.578 )	-1.71 ( 3.450 )	0.43 ( 1.988 )	-1.00 ( 2.828 )	1.00 ( 99999 )
Change in Cholesterol (n=4,5,7,2,4,5,7,1)	0.45 ( 0.191 )	-0.55 ( 0.583 )	0.52 ( 1.102 )	1.48 ( 1.369 )	-0.02 ( 0.505 )	0.19 ( 0.578 )	0.58 ( 0.311 )	0.83 ( 99999 )
Change in Glucose (n=2,4,2,0,2,4,5,0)	-0.42 ( 0.898 )	0.34 ( 1.096 )	0.78 ( 0.668 )	0.18 ( 0.249 )	-0.24 ( 1.450 )	-0.07 ( 0.640 )	99999 ( 99999 )	99999 ( 99999 )
Change in Phosphate (n=4,2,7,2,4,2,7,1)	-0.22 ( 0.277 )	0.05 ( 0.169 )	0.11 ( 0.339 )	0.16 ( 0.042 )	-0.00 ( 0.154 )	-0.08 ( 0.145 )	-0.31 ( 0.714 )	0.07 ( 99999 )
Change in Potassium (n=4,5,7,2,4,5,7,1)	-0.23 ( 0.222 )	-0.10 ( 0.712 )	0.06 ( 0.167 )	-0.02 ( 0.669 )	0.19 ( 0.652 )	0.21 ( 0.285 )	0.25 ( 0.212 )	-0.60 ( 99999 )
Change in Sodium (n=4,5,7,2,4,5,7,1)	1.25 ( 2.986 )	0.50 ( 3.109 )	0.00 ( 2.236 )	-0.40 ( 2.408 )	-1.86 ( 2.911 )	1.14 ( 0.690 )	4.00 ( 4.243 )	-2.00 ( 99999 )
Change in Triglycerides (n=4,5,7,2,4,5,7,1)	0.94 ( 0.619 )	0.54 ( 0.602 )	-0.50 ( 0.641 )	-0.05 ( 0.910 )	0.27 ( 1.047 )	-0.09 ( 0.544 )	0.44 ( 0.156 )	0.05 ( 99999 )
Change in Urea Nitrogen (n=4,5,7,2,4,5,7,1)	0.27 ( 0.791 )	1.69 ( 0.942 )	0.74 ( 1.440 )	0.89 ( 3.316 )	-0.97 ( 1.296 )	0.61 ( 1.694 )	0.18 ( 1.768 )	0.36 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate

End point description

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. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	7	7	2	1
Units: mcmol/L
arithmetic mean (standard deviation)
Change in Creatinine	2.25 ( 4.505 )	6.51 ( 8.187 )	1.80 ( 4.024 )	3.61 ( 4.929 )	-1.28 ( 3.402 )	1.29 ( 3.400 )	4.51 ( 6.357 )	9.00 ( 99999 )
Change in Direct Bilirubin	0.00 ( 0.000 )	0.00 ( 0.000 )	0.08 ( 0.183 )	0.08 ( 0.183 )	0.00 ( 0.000 )	0.00 ( 0.000 )	0.00 ( 0.000 )	0.00 ( 99999 )
Change in Urate	0.00 ( 0.024 )	-0.01 ( 0.054 )	-0.02 ( 0.064 )	0.01 ( 0.086 )	-0.02 ( 0.032 )	-0.00 ( 0.045 )	0.01 ( 0.097 )	0.04 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein

End point description

Albumin, globulin, protein were expressed as g/L. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	7	7	2	1
Units: g/L
arithmetic mean (standard deviation)
Change in Albumin	0.50 ( 1.291 )	2.00 ( 3.266 )	2.00 ( 4.183 )	5.60 ( 7.335 )	-0.29 ( 2.059 )	-0.29 ( 2.870 )	-1.00 ( 4.243 )	2.00 ( 99999 )
Change in Globulin	2.50 ( 6.455 )	7.25 ( 8.057 )	-2.20 ( 3.114 )	0.20 ( 3.347 )	0.71 ( 1.496 )	3.43 ( 2.760 )	-2.00 ( 2.828 )	3.00 ( 99999 )
Change in Protein	3.00 ( 5.657 )	9.25 ( 9.287 )	-0.20 ( 2.588 )	5.80 ( 7.596 )	0.43 ( 3.047 )	3.14 ( 3.934 )	-3.00 ( 7.071 )	5.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

End point description

SBP and DBP were measured after the subject 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. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint. Here, "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	3	5	5	9	8	3	1
Units: mmHg
arithmetic mean (standard deviation)
Change in SBP	-1.00 ( 26.211 )	27.00 ( 30.199 )	0.60 ( 6.066 )	4.00 ( 5.477 )	0.33 ( 19.780 )	10.63 ( 20.333 )	10.33 ( 4.726 )	16.00 ( 99999 )
Change in DBP	-5.33 ( 3.786 )	23.00 ( 20.298 )	4.40 ( 5.857 )	1.60 ( 5.941 )	-0.89 ( 10.659 )	6.00 ( 9.885 )	8.67 ( 6.429 )	0.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate

End point description

Pulse rate measured after the subject 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. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	8	3	1
Units: beats/min
arithmetic mean (standard deviation)	5.25 ( 16.112 )	-9.25 ( 14.773 )	-4.40 ( 7.537 )	-15.80 ( 11.670 )	-14.89 ( 14.675 )	-13.75 ( 9.543 )	-21.67 ( 21.127 )	-26.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate

End point description

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. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	3	5	5	9	8	3	1
Units: breaths/min
arithmetic mean (standard deviation)	-5.33 ( 6.110 )	-4.33 ( 7.506 )	-3.00 ( 4.183 )	-4.80 ( 5.541 )	-4.78 ( 8.243 )	-3.88 ( 7.415 )	-5.33 ( 2.309 )	6.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature

End point description

Body temperature was expressed as degree centigrade. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	3	5	5	9	8	3	1
Units: degree centigrade
arithmetic mean (standard deviation)	0.10 ( 0.265 )	0.47 ( 0.702 )	-0.02 ( 0.130 )	0.02 ( 0.045 )	0.02 ( 0.199 )	-0.16 ( 0.311 )	0.13 ( 0.153 )	-0.20 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Height

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Height

End point description

Height was expressed as centimeters. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	8	2	1
Units: centimeters
arithmetic mean (standard deviation)	4.76 ( 2.197 )	17.65 ( 3.643 )	5.20 ( 2.361 )	12.78 ( 2.548 )	5.06 ( 1.429 )	10.24 ( 1.849 )	3.63 ( 1.237 )	6.50 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Weight

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Weight

End point description

Weight was expressed as kilograms. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	8	3	1
Units: kilograms
arithmetic mean (standard deviation)	1.88 ( 0.377 )	3.88 ( 2.081 )	1.20 ( 1.065 )	3.24 ( 1.356 )	1.01 ( 1.134 )	2.88 ( 1.792 )	0.77 ( 0.153 )	0.90 ( 99999 )

No statistical analyses for this end point

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

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End point title

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

End point description

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. SAS: subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed"=subjects evaluable for this endpoint and "n"= subjects evaluable for specified categories. "99999"= data could not be calculated for 1 subject.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	7	3	1
Units: msec
arithmetic mean (standard deviation)
Single Beat QTcB Interval (n=4,5,8,3,4,5,6,1)	-9.0 ( 24.06 )	-29.75 ( 27.476 )	-7.0 ( 26.29 )	-5.60 ( 32.168 )	-3.8 ( 33.86 )	4.33 ( 8.710 )	17.0 ( 14.42 )	58.00 ( 99999 )
Single Beat QTcF Interval (n=4,5,8,3,4,5,6,1)	-4.5 ( 20.86 )	-8.25 ( 22.721 )	-10.0 ( 21.99 )	-2.40 ( 36.115 )	1.9 ( 29.95 )	1.17 ( 9.347 )	5.7 ( 8.62 )	27.00 ( 99999 )
Single Beat PR Interval (n=4,5,8,3,4,5,6,1)	-2.8 ( 4.57 )	3.00 ( 3.162 )	-2.8 ( 8.47 )	3.80 ( 13.236 )	-1.1 ( 16.66 )	2.50 ( 8.689 )	-10.3 ( 12.66 )	-3.00 ( 99999 )
Single Beat QRS Duration (n=4,5,8,3,4,5,6,1)	-0.5 ( 5.45 )	3.75 ( 2.986 )	-0.2 ( 5.89 )	-1.20 ( 6.181 )	-0.8 ( 3.20 )	-1.67 ( 3.830 )	-6.0 ( 8.00 )	1.00 ( 99999 )
Aggregate RR Interval (n=4,5,9,3,4,5,7,1)	28.3 ( 35.36 )	165.25 ( 31.127 )	-30.4 ( 26.37 )	23.00 ( 72.087 )	60.7 ( 61.84 )	20.57 ( 81.506 )	-76.7 ( 77.36 )	-178.00 ( 99999 )
Single Beat QT Interval (n=4,5,8,3,4,5,6,1)	1.8 ( 17.23 )	23.25 ( 14.569 )	-13.8 ( 16.04 )	2.40 ( 41.374 )	10.6 ( 29.61 )	-3.17 ( 15.779 )	-10.0 ( 18.33 )	-16.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference

End point description

Head circumference was expressed as centimeters. Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	8	2	1
Units: centimeters
arithmetic mean (standard deviation)	1.87 ( 1.231 )	4.02 ( 0.846 )	1.50 ( 1.061 )	2.50 ( 0.791 )	1.14 ( 1.927 )	2.36 ( 1.537 )	-0.15 ( 0.495 )	0.50 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in ECG Parameter: ECG Ventricular Rate

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in ECG Parameter: ECG Ventricular Rate

End point description

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. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	4	4	5	5	9	7	3	1
Units: beats/min
arithmetic mean (standard deviation)	-7.5 ( 9.04 )	-36.25 ( 4.272 )	8.6 ( 7.37 )	-4.40 ( 15.437 )	-12.2 ( 11.39 )	-3.14 ( 17.837 )	18.7 ( 22.85 )	50.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin

End point description

Thyrotropin was expressed as milli-international units per liter (mIU/L). Change from Baseline was calculated as post-Baseline absolute value minus Baseline value. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	4	3	5	5	6	1	1
Units: mIU/L
arithmetic mean (standard deviation)	1.12 ( 1.242 )	0.05 ( 0.590 )	-1.02 ( 0.279 )	-0.89 ( 1.405 )	1.33 ( 1.283 )	-0.08 ( 1.026 )	-0.90 ( 99999 )	-0.35 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)

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End point title

Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)

End point description

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. Mean change from baseline data for specified parameter was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	1	3	3	4	5	7	1	1
Units: mmol/L*10^-6
arithmetic mean (standard deviation)	-2.00 ( 99999 )	6.00 ( 0.000 )	7.00 ( 3.606 )	4.75 ( 5.439 )	3.60 ( 6.066 )	6.29 ( 9.160 )	1.00 ( 99999 )	-1.00 ( 99999 )

No statistical analyses for this end point

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Free Thyroxine, and Free Triiodothyronine

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End point title

Core Phase and Extension Phase: Mean Change from Baseline in Free Thyroxine, and Free Triiodothyronine

End point description

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. Mean change from baseline data for specified parameters was reported. The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. Here, "Number of Subjects Analyzed" signifies subjects who were evaluable for this endpoint and "99999" signifies standard deviation could not be calculated as 1 subject was available for the analysis.

End point type

Secondary

End point timeframe

Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

End point values	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Number of subjects analysed	3	4	1	3	5	5	1	1
Units: pmol/L
arithmetic mean (standard deviation)
Change in Free Thyroxine	0.90 ( 1.931 )	2.55 ( 1.021 )	-1.30 ( 99999 )	0.83 ( 1.443 )	-1.80 ( 1.147 )	0.00 ( 0.919 )	-3.90 ( 99999 )	-3.90 ( 99999 )
Change in Free Triiodothyronine	-0.40 ( 0.889 )	0.28 ( 1.250 )	0.60 ( 99999 )	1.03 ( 0.611 )	0.06 ( 0.885 )	-0.16 ( 1.230 )	-4.30 ( 99999 )	-1.80 ( 99999 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse event reporting additional description

The SAS was the group of subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Reporting group description

Subjects 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Reporting group title

Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Reporting group description

Subjects 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Reporting group title

Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Reporting group description

Reporting group title

Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel

Reporting group description

Reporting group title

Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel

Reporting group description

Subjects 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Reporting group title

Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel

Reporting group description

Subjects 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 subjects who are not taking any EIAED), or titrated up to a maximum of 16 mg/day (for subjects who are taking any EIAED). Dose titration was up to Week 12 for Non-EIAED subjects and up to Week 16 for EIAED subjects to identify each subject's optimum dose during Core Phase. Subjects then continued to take perampanel at optimal dose level 12 mg/day (for Non-EIAED subjects or 16 mg/day (for EIAED subjects) as a maintenance dose for up to 4 weeks during Core Phase. The total treatment duration of Core Phase was up to 16 weeks for non-EIAED subjects or up to 20 weeks for EIAED subjects.

Serious adverse events	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 4 (50.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	3 / 4 (75.00%)	1 / 5 (20.00%)	3 / 8 (37.50%)	1 / 5 (20.00%)	1 / 3 (33.33%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Nervous system disorders
Epilepsy
subjects affected / exposed	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	2 / 2	2 / 2	5 / 5	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Aspiration
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental Status Changes
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	2 / 2	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bullous impetigo
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenovirus Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Syncytial Virus Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Covid-19
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterovirus Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Parainfluenzae Virus Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia Aspiration
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia Bacterial
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Syncytial Virus Bronchiolitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Tract Infection Viral
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Failure To Thrive
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Core Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Core Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Extension Phase, Cohort 4, Age >=24 to <48 Months: Perampanel	Extension Phase, Cohort 1, Age >=1 to <=6 Months: Perampanel	Extension Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Extension Phase, Cohort 3, Age >12 to <24 Months: Perampanel	Core Phase, Cohort 2, Age >6 to <=12 Months: Perampanel	Core Phase, Cohort 4, Age >=24 to <48 Months: Perampanel
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 4 (50.00%)	9 / 9 (100.00%)	1 / 1 (100.00%)	2 / 4 (50.00%)	5 / 5 (100.00%)	8 / 8 (100.00%)	5 / 5 (100.00%)	2 / 3 (66.67%)
Investigations
Oxygen Saturation Decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0
Gamma-Glutamyltransferase Increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Injury, poisoning and procedural complications
Lip Injury
subjects affected / exposed	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	0	0	0	0	1
Skin Laceration
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Nervous system disorders
Balance Disorder
subjects affected / exposed	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	1	0	0	0	0	1
Seizure
subjects affected / exposed	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	1	2	0
Somnolence
subjects affected / exposed	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 3 (0.00%)
occurrences all number	0	3	0	0	0	2	2	0
Ataxia
subjects affected / exposed	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0
Status Epilepticus
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 4 (25.00%)	5 / 9 (55.56%)	1 / 1 (100.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	3 / 8 (37.50%)	0 / 5 (0.00%)	2 / 3 (66.67%)
occurrences all number	1	9	2	1	0	3	0	2
Hypothermia
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Ear and labyrinth disorders
Ear Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Immune system disorders
Food Allergy
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	2 / 9 (22.22%)	1 / 1 (100.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 8 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)
occurrences all number	0	3	1	0	1	2	1	1
Vomiting
subjects affected / exposed	0 / 4 (0.00%)	3 / 9 (33.33%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	1 / 3 (33.33%)
occurrences all number	0	5	1	0	0	1	1	1
Dyspepsia
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Teething
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Nausea
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Faecaloma
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Asthma
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Adenoidal Hypertrophy
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Nasal Congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0
Psychiatric disorders
Aggression
subjects affected / exposed	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Insomnia
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	0 / 4 (0.00%)	3 / 9 (33.33%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	2 / 8 (25.00%)	3 / 5 (60.00%)	1 / 3 (33.33%)
occurrences all number	0	4	0	0	4	2	4	2
Rhinitis
subjects affected / exposed	1 / 4 (25.00%)	3 / 9 (33.33%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	3	0	0	0	1	0	0
Sinusitis
subjects affected / exposed	1 / 4 (25.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 4 (0.00%)	4 / 9 (44.44%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	8	0	2	0	3	0	0
Gastroenteritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Ear Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Bronchitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Gastroenteritis Viral
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Influenza
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Pharyngitis Streptococcal
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Rotavirus Infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Pneumonia Aspiration
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Product issues
Device Dislocation
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Vitamin D Deficiency
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Malnutrition
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Failure To Thrive
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Dehydration
subjects affected / exposed	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 Feb 2017

Amendment 01: Changed the gestational age from 41 to 36 weeks in inclusion criterion 1; Removed 4-week time frame of last seizure occurrence prior to Visit 1 from inclusion criterion 5; Changed seizure surgery restriction from “before Visit 1” to “within 1 year of Visit 1” in exclusion criterion 4.

09 Apr 2020

Amendment 2: For non-EIAED subjects, target perampanel dose was lowered to 4 mg/day. Depending upon individual clinical response and tolerability, non-EIAED subjects could still have their perampanel dose up-titrated to 6 mg/day. Added a cohort of subjects from 2 to less than 4 years of age and specified total number of subjects required when pooled across multiple studies; Made editorial changes to study endpoints; Increased overall study duration; Deleted Clinical Global Impression of Severity (CGI-S) from exploratory objectives and endpoints; Increased the allowed number of concomitant anti-epileptic drugs (AEDs) from 3 to 4; Lowered the target dose to 6 mg/day for non-enzyme-inducing anti-epileptic drug (non-EIAED) and to 8 mg/day for EIAED subjects; Specified conditions for further up-titrations to maximum allowed doses up to 12 mg/day for non-EIAED and 16 mg/day for EIAED subjects; Modified the period during which concomitant AED doses must have remained stable for eligibility determination; Modified the period during which concomitant central nervous system (CNS) drugs must have remained stable, and specified that these drugs are prohibited throughout the course of the study; Modified exclusion criterion related to prior or concomitant use of felbamate and vigabatrin and specified that these drugs are prohibited throughout the course of the study.

09 Apr 2020

Amendment 02 (continued): Modified the exclusion criterion related to prior use of perampanel; Specified that concomitant use of cannabidiol (CBD) products is allowed; Modified concomitant therapy section to allow dose adjustments of concomitant AEDs (non-enzyme inducing AEDs only) during the Core study. AED addition or deletion will remain prohibited during the Core Study; Specified that the subjects who immediately switch to commercially available perampanel after the last dose of study drug at the end of Core Study or Extension Phase need not undergo Follow-up Period/Visit; Added description of sample size calculations for the 2 to less than 4 years of age group; Lipid and blood glucose tests are to be collected under fasting conditions, whenever practically feasible, at all-time points; Clarified baseline seizure frequency data for efficacy endpoint analyses; Added early PK sampling time points at predose and 1 to 5 hours postdose for subjects of 2 to less than 4 years of age and adjusted dosing instructions around PK visits during Maintenance Period. Added a statement that the dose-normalized derived exposure parameters will be summarized for age groups.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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 Subjects

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 Subjects

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

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

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

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

Primary: Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Primary: Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Subjects

Secondary: Core Phase and Extension Phase: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Secondary: Core Phase and Extension Phase: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Erythrocytes

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Erythrocytes

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Hemoglobin

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Hematology Laboratory Parameter: Hemoglobin

Secondary: 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

Secondary: 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

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Height

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Height

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Weight

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Weight

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

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

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in ECG Parameter: ECG Ventricular Rate

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in ECG Parameter: ECG Ventricular Rate

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)

Secondary: Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Free Thyroxine, and Free Triiodothyronine

Secondary: Core Phase and Extension Phase: Mean Change from Baseline in Free Thyroxine, and Free Triiodothyronine

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
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