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Clinical Trial Results:
An Open-Label, Multicenter Study With an Extension Phase to Evaluate the Safety, Tolerability, and Exposure-Efficacy Relationship of Perampanel Oral Suspension When Administered as an Adjunctive Therapy in Pediatric Subjects (Age 4 to Less Than 12 Years) With Inadequately Controlled Partial-Onset Seizures or Primary Generalized Tonic-Clonic Seizures

Summary
EudraCT number	2014-002167-16
Trial protocol	HU LV ES PL BE IT Outside EU/EEA
Global end of trial date	06 Dec 2021

Results information
Results version number	v1(current)
This version publication date	17 Jun 2022
First version publication date	17 Jun 2022
Other versions

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-G000-311

ISRCTN number

US NCT number

NCT02849626

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 Europe Ltd., +44 (0)208 600 1400, EUMedInfo@eisai.net

Scientific contact

EMEA Medical Information, Eisai Europe 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

06 Dec 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

This is an open-label, multicenter study with an Extension Phase to evaluate the safety and tolerability of perampanel oral suspension when administered as an adjunctive therapy in children (ages 4 to less than [<] 12 years) with inadequately controlled partial onset seizures (POS) or primary generalized tonic clonic (PGTC) seizures.

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

16 Nov 2016

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

1 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 5

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

Hungary: 26

Country: Number of subjects enrolled

Japan: 65

Country: Number of subjects enrolled

Latvia: 6

Country: Number of subjects enrolled

Poland: 16

Country: Number of subjects enrolled

Korea, Republic of: 1

Country: Number of subjects enrolled

Spain: 14

Country: Number of subjects enrolled

United States: 37

Worldwide total number of subjects

180

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)

180

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 at 58 sites in the United States, European Union, Asia Pacific. 208 subjects were screened/enrolled. Of which 28 screen failures and 180 received treatment in Core Phase. Of 146 who completed Core Phase, 136 entered Extension Phase A. Of 122 who completed Extension Phase A, 42 entered Extension Phase B and 41 received treatment.

Screening details

This study included a Core Phase and two Extension Phases (Extension Phase A and Extension Phase B).

Period 1 title

Core Phase (up to 23 weeks)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Perampanel 0.5 mg/mL: POS

Arm description

Core Phase: Subjects with partial onset-seizures (POS) received perampanel 0.5 milligrams per milliliter (mg/mL) oral suspension titrated beyond 8 milligram per day (mg/day) up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any enzyme-inducing antiepileptic drug [EIAED]), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject’s optimum dose. Subjects then continued to take perampanel once daily at optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed Core Phase, entered Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral drops, suspension

Routes of administration

Oral use

Dosage and administration details

Perampanel 0.5 mg/mL oral suspension

Perampanel 0.5 mg/mL: PGTC Seizures

Arm description

Core Phase: Subjects with primary generalized tonic clonic (PGTC) seizures received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any other EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject’s optimum dose. Subjects then continued to take perampanel oral suspension once daily at the optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed the Core Phase, entered the Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral drops, suspension

Routes of administration

Oral use

Dosage and administration details

Perampanel 0.5 mg/mL oral suspension

Number of subjects in period 1	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Started	149	31
Completed	122	24
Not completed	27	7
Inadequate Therapeutic Effect	6	2
Consent withdrawn by subject	7	2
Non-specified	3	-
Adverse event, non-fatal	11	3

Period 2 title

Extension Phase A (up to 29 weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Perampanel 0.5 mg/mL: POS

Arm description

Core Phase: Subjects with POS received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any [EIAED]), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject’s optimum dose. Subjects then continued to take perampanel once daily at optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed Core Phase, entered Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral drops, suspension

Routes of administration

Oral use

Dosage and administration details

Perampanel 0.5 mg/mL oral suspension

Perampanel 0.5 mg/mL: PGTC Seizures

Arm description

Core Phase: Subjects with PGTC seizures received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any other EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject's optimum dose. Subjects then continued to take perampanel oral suspension once daily at the optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed the Core Phase, entered the Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral drops, suspension

Routes of administration

Oral use

Dosage and administration details

Perampanel 0.5 mg/mL oral suspension

Number of subjects in period 2 ^[1]	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Started	116	20
Completed	105	17
Not completed	11	3
Inadequate Therapeutic Effect	3	1
Consent withdrawn by subject	4	-
Non-specified	1	-
Adverse event, non-fatal	3	2

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only eligible participants who completed Core Phase entered into Extension Phase A.

Period 3 title

Extension Phase B (up to 89 weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Extension B: Perampanel 0.5 mg/mL: POS

Arm description

Subjects who completed Core Phase and Extension Phase A entered Extension Phase B, and continued with their optimal perampanel dose from Core Phase until a subject reached 12 years of age, switched to the commercial perampanel product, or discontinued for safety or administrative reasons.

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral drops, suspension

Routes of administration

Oral use

Dosage and administration details

Perampanel 0.5 mg/mL oral suspension

Extension B: Perampanel 0.5 mg/mL: PGTC Seizures

Arm description

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

Other name

E2007

Pharmaceutical forms

Oral drops, suspension

Routes of administration

Oral use

Dosage and administration details

Perampanel 0.5 mg/mL oral suspension

Number of subjects in period 3 ^[2]	Extension B: Perampanel 0.5 mg/mL: POS	Extension B: Perampanel 0.5 mg/mL: PGTC Seizures
Started	41	1
Completed	36	1
Not completed	5	0
Inadequate Therapeutic Effect	3	-
Unspecified	1	-
Subject choice	1	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only eligible participants who completed Core Phase and Extension A entered into Extension Phase B.

Baseline characteristics

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Reporting group title

Perampanel 0.5 mg/mL: POS

Reporting group description

Reporting group title

Perampanel 0.5 mg/mL: PGTC Seizures

Reporting group description

Reporting group values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures	Total
Number of subjects	149	31	180
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	149	31	180
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	0	0	0
From 65-84 years	0	0	0
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	8.1 ( 2.10 )	8.5 ( 2.03 )	-
Sex: Female, Male
Units: subjects
Female	77	11	88
Male	72	20	92
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	3	7	10
Not Hispanic or Latino	141	19	160
Unknown or Not Reported	5	5	10
Race/Ethnicity, Customized
Units: Subjects
White	70	23	93
Black or African American	2	1	3
Japanese	65	0	65
Other Asian	5	1	6
American Indian or Alaska Native	1	0	1
Other	2	1	3
Missing	4	5	9

End points

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Reporting group title

Perampanel 0.5 mg/mL: POS

Reporting group description

Reporting group title

Perampanel 0.5 mg/mL: PGTC Seizures

Reporting group description

Reporting group title

Perampanel 0.5 mg/mL: POS

Reporting group description

Reporting group title

Perampanel 0.5 mg/mL: PGTC Seizures

Reporting group description

Reporting group title

Extension B: Perampanel 0.5 mg/mL: POS

Reporting group description

Reporting group title

Extension B: Perampanel 0.5 mg/mL: PGTC Seizures

Reporting group description

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Core Phase: Subjects with POS or PGTC seizures received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject's optimum dose. Subjects then continued to take perampanel once daily at optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed Core Phase, entered Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Core Phase: Subjects with POS or PGTC seizures received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject’s optimum dose. Subjects then continued to take perampanel once daily at optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed Core Phase, entered Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Perampanel: POS

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects with POS who received perampanel 0.5 mg/mL oral suspension (for subjects with age less than [<] 12 years) or tablets (for subjects with age >=12 years) titrated to a dose of up to 8 mg/day for up to 23 weeks in studies E2007-G000-304 (NCT00699972), E2007-G000-305 (NCT00699582), E2007-G000-306 (NCT00700310), E2007-J000-335 (NCT01618695) and this current study (E2007-G000-311).

Subject analysis set title

Perampanel: PGTC Seizures

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects with PGTC seizures who received perampanel 0.5 mg/mL oral suspension (for subjects with age <12 years) or tablets (for subjects with age >=12 years) titrated to a dose of up to 8 mg/day for up to 23 weeks in studies E2007-G000-232 (NCT01527006) and E2007-G000-332 (NCT01393743) and this current study (E2007-G000-311).

Subject analysis set title

Perampanel: Subjects aged (<12 years)

Subject analysis set type

Safety analysis

Subject analysis set description

All non-Asian subjects with POS, received perampanel oral suspension (subjects with age <12 years) titrated to a dose of up to 8 mg/day or up to 12 mg/day for up to 23 weeks in this current study E2007-G000-311.

Subject analysis set title

Perampanel: Subjects aged (>=12 years)

Subject analysis set type

Safety analysis

Subject analysis set description

All non-Asian subjects with POS, received perampanel tablets (subjects with age >=12 years) titrated to a dose of up to 8 mg/day or up to 12 mg/day for up to 23 weeks in studies E2007-G000-304 (NCT00699972), E2007-G000-305 (NCT00699582), E2007-G000-306 (NCT00700310), E2007-J000-335 (NCT01618695).

Subject analysis set title

Perampanel: Without Topiramate

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects with PGTC seizures received perampanel as oral suspension (aged <12 years) or as oral tablets (aged >=12 years) titrated to a dose of up to 8 mg/day or up to 12 mg/day without topiramate for up to 23 weeks in studies E2007-G000-232 (NCT01527006) and E2007-G000-332 (NCT01393743) and this current study (E2007-G000-311).

Subject analysis set title

Perampanel: With Topiramate

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects with PGTC seizures received perampanel as oral suspension (aged <12 years) or as oral tablets (aged >=12 years) titrated to a dose of up to 8 mg/day or up to 12 mg/day along with topiramate for up to 23 weeks in studies E2007-G000-232 (NCT01527006) and E2007-G000-332 (NCT01393743) and this current study (E2007-G000-311).

Subject analysis set title

Perampanel: POS

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects with POS who received perampanel 0.5 mg/mL oral suspension (for subjects with age <12 years) or tablets (for subjects with age >=12 years) titrated to a dose of up to 8 mg/day for up to 23 weeks in studies E2007-G000-304 (NCT00699972), E2007-G000-305 (NCT00699582), E2007-G000-306 (NCT00700310), E2007-J000-335 (NCT01618695) and this current study (E2007-G000-311).

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Perampanel 0.5 mg/mL: All Subjects

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Perampanel 0.5 mg/mL: 4 to <7 Years

Subject analysis set type

Full analysis

Subject analysis set description

Core Phase: Subjects of age 4 to <7 years with POS or PGTC seizures received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject's optimum dose. Subjects then continued to take perampanel once daily at optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed Core Phase, entered Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Subject analysis set title

Perampanel 0.5 mg/mL: 7 to <12 Years

Subject analysis set type

Full analysis

Subject analysis set description

Core Phase: Subjects of age 7 to <12 years with POS or PGTC seizures received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any other EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject's optimum dose. Subjects then continued to take perampanel oral suspension once daily at the optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed the Core Phase, entered the Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Primary: Percentage of Subjects With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Subjects - Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Subjects - Core Phase and Extension Phase A of This Study ^[1]

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Primary

End point timeframe

Baseline up to 4 weeks (follow up in Extension Phase A) after last dose of study drug in Extension Phase A at Week 52 (up to 56 weeks)

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: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	180
Units: percentage of subjects
number (not applicable)
Treatment Emergent AEs	90.0
Treatment Emergent SAEs	20.0

No statistical analyses for this end point

Primary: Percentage of Subjects With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Subjects - Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Subjects - Core Phase and Extension Phase A of This Study ^[2]

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Primary

End point timeframe

Baseline up to 52 weeks

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: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	180
Units: percentage of subjects
number (not applicable)
Potassium: Markedly Abnormal High (n=177)	0.6
Sodium: Markedly Abnormal Low (n=177)	1.1
Alanine Aminotransferase: Abnormal High (n=177)	1.1
Calcium: Abnormal Low (n=177)	0.6
Gamma Glutamyl Transferase: Abnormal High (n=177)	2.8
Neutrophils: Abnormal Low (n=176)	9.1
Hemoglobin: Abnormal Low (n=176)	1.7
Leukocytes: Abnormal Low (n=176)	0.6

No statistical analyses for this end point

Primary: Percentage of Subjects With Abnormal Vital Sign Values for Total Group of Subjects- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Abnormal Vital Sign Values for Total Group of Subjects- Core Phase and Extension Phase A of This Study ^[3]

End point description

Pre-defined criteria of vital signs abnormalities: maximum (max.) increase or decrease from baseline in sitting/supine systolic blood pressure (SBP) of greater than or equal to (>=) 20 or 40 millimeter of mercury (mmHg); maximum increase or decrease from baseline in sitting/supine diastolic blood pressure (DBP) >=10 or 20 mmHg; increase or decrease from baseline in pulse rate (number of heart beats per minute [bpm]) of >=15 or 30 bpm. Data for this outcome measure has been assessed and reported till Week 52. SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subjects analyzed" signifies subjects who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline up to 52 weeks

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: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	179
Units: percentage of subjects
number (not applicable)
Systolic Blood Pressure: Increment >=20 mmHg	24.6
Systolic Blood Pressure: Increment >=40 mmHg	2.2
Systolic Blood Pressure: Decrement >=20 mmHg	20.1
Systolic Blood Pressure: Decrement >=40 mmHg	0.6
Diastolic Blood Pressure: Increment >=10 mmHg	48.0
Diastolic Blood Pressure: Increment >=20 mmHg	26.8
Diastolic Blood Pressure: Decrement >=10 mmHg	38.0
Diastolic Blood Pressure: Decrement >=20 mmHg	16.8
Pulse: Increment >=15 bpm	35.8
Pulse: Increment >=30 bpm	11.7
Pulse: Decrement >=15 bpm	39.7
Pulse: Decrement >=30 bpm	13.4

No statistical analyses for this end point

Primary: Percentage of Subjects With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Subjects - Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Subjects - Core Phase and Extension Phase A of This Study ^[4]

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subjects analyzed" signifies subjects who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline up to 52 weeks

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: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	174
Units: percentage of subjects
number (not applicable)
QTc Bazett: Increase of >30 millisecond (msec)	8.0
QTc Bazett: Increase of >60 msec	0
QTc Bazett: >450 msec	4.0
QTc Bazett: >480 msec	0
QTc Bazett: >500 msec	0
QTc Fridericia: Increase of >30 msec	5.2
QTc Fridericia: Increase of >60 msec	0
QTc Fridericia: >450 msec	0
QTc Fridericia: >480 msec	0
QTc Fridericia: >500 msec	0

No statistical analyses for this end point

Secondary: Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL)

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End point title

Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL)

End point description

Seizure frequency was derived from information recorded in subject diary. Seizure frequency per 28 days calculated as number of seizures divided by number of days in the interval and multiplied by 28. Due to sparse pharmacokinetic (PK) sampling, data of OM was analyzed by pooling data from other Phase II/III studies of perampanel along with data of current study, subjects with POS or PGTC. Only data for subjects taking perampanel 8 mg/day (Cav, ss of 518 ng/mL) were reported. Subjects taking perampanel 12 mg/day in the studies from which data were pooled, were not included in analysis. ng/mL refers to nanogram per milliliter. Data for this OM was calculated through model prediction. All subjects who received perampanel who have seizure frequency, cognition, or AE data with documented dosing history. Population for this OM included subjects from other studies as well subjects from current study. Here "number of subject analyzed" signifies subjects evaluable for this measure.

End point type

Secondary

End point timeframe

Baseline, Week 23

End point values	Perampanel: POS	Perampanel: PGTC Seizures
Number of subjects analysed	1371	92
Units: percent change
number (not applicable)	-43.1	-63.6

No statistical analyses for this end point

Secondary: Overall Responder Probability For Non-Asian Subjects With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

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End point title

Overall Responder Probability For Non-Asian Subjects With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

End point description

For this OM, responders were those who experienced a 50 percent (%) or greater reduction in seizure frequency per 28 days from baseline. Due to the sparse PK sampling in this study, the data of this OM were pooled with data from other Phase III studies of perampanel conducted in subjects with POS. “AEDs not affecting PK” refers to AEDs not affecting PK of perampanel. Data for this OM has been reported for only non-Asian subjects with POS per age groups. Responder probability has been reported for Cav,ss of perampanel when given along with different antiepileptic drugs (AEDs). All subjects who received perampanel who have seizure frequency, cognition, or AE data with documented dosing history. Population for this OM included subjects from other studies as well subjects from this current study. Here "number of subjects analyzed" signifies subjects who were evaluable for this measure.

End point type

Secondary

End point timeframe

Baseline up to 23 weeks

End point values	Perampanel: Subjects aged (<12 years)	Perampanel: Subjects aged (>=12 years)
Number of subjects analysed	123	1420
Units: Responder probability
number (not applicable)
8 mg/day+ AEDs not affecting PK:Cav ss 518 ng/mL	0.605	0.466
12 mg/day+ AEDs not affecting PK:Cav ss 778 ng/mL	0.669	0.535
8 mg/day+ Oxcarbazepine/Phenytoin:Cav ss 258 ng/mL	0.520	0.382
12 mg/day+Oxcarbazepine/Phenytoin:Cav ss 387 ng/mL	0.565	0.426
8 mg/day+ Carbamazepine:Cav ss 175 ng/mL	0.485	0.350
12 mg/day+ Carbamazepine:Cav ss 263 ng/mL	0.522	0.384

No statistical analyses for this end point

Secondary: Overall Responder Probability For Subjects With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

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End point title

Overall Responder Probability For Subjects With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

End point description

For this OM, responders were those who experienced a 50% or greater reduction in seizure frequency per 28 days from baseline. Due to the sparse PK sampling in this study, the data of this OM were analyzed by pooling the data from other Phase II and III studies of perampanel along with data of this current study, including subjects with PGTC seizures. In this outcome measure, responder probability at different concentration values of perampanel when given with or without topiramate (an antiepileptic) has been reported to compare the effect of topiramate on responder probability. All subjects who received perampanel who have seizure frequency, cognition, or AE data with documented dosing history. Population for this measure included subjects from other studies as well subjects from this current study. Here "number of subjects analyzed" signifies subjects who were evaluable for this measure.

End point type

Secondary

End point timeframe

Baseline up to 23 weeks

End point values	Perampanel: Without Topiramate	Perampanel: With Topiramate
Number of subjects analysed	138	31
Units: Responder probability
number (not applicable)
0 ng/mL	0.46	0.26
100 ng/mL	0.71	0.50
200 ng/mL	0.74	0.54
300 ng/mL	0.76	0.57
400 ng/mL	0.77	0.58
500 ng/mL	0.78	0.59
600 ng/mL	0.79	0.60
700 ng/mL	0.80	0.61
800 ng/mL	0.80	0.62
900 ng/mL	0.80	0.63
1000 ng/mL	0.81	0.63
1200 ng/mL	0.82	0.64
1400 ng/mL	0.82	0.65
1600 ng/mL	0.82	0.66
1800 ng/mL	0.83	0.66
2000 ng/mL	0.83	0.67
2200 ng/mL	0.84	0.67
2400 ng/mL	0.84	0.68

No statistical analyses for this end point

Secondary: Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

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End point title

Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

End point description

Due to the sparse PK sampling in this study, the data of this OM were analyzed by pooling data from other Phase II and III studies of perampanel along with this current study, including subjects with POS or PGTC. Data for this OM have been reported in relationship with different ranges of Cav, ss of Perampanel as “number of observations” those were seizure free for up to 3 visits. The reason for using number of observations for analysis of this OM was because data were available as up to 3 visits per subjects and not necessarily that the subject was seizure-free on all three visits. All subjects who received perampanel who have seizure frequency, cognition, or AE data with documented dosing history. Population for this measure included subjects from other studies as well subjects from this current study. Here "number of subjects analyzed" signifies subjects who were evaluable for this measure and SFO denotes Seizure free observations.

End point type

Secondary

End point timeframe

Baseline up to Week 23

End point values	Perampanel: POS	Perampanel: PGTC Seizures
Number of subjects analysed	1371	92
Units: Seizure free observations
>0 - <500 ng/mL(3189,127:POS/PGTC SFO)	275	57
500 - <1000 ng/mL(583,104:POS/PGTC SFO)	103	67
1000 - <1500 ng/mL(159,15:POS/PGTC SFO)	33	11
1500 - 2000 ng/mL(33,6:POS/PGTC SFO)	7	4
>2000 ng/mL(10,3:POS/PGTC SFO)	0	3

No statistical analyses for this end point

Secondary: Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of this Study: Assessment Based on Relationship With Plasma Levels of Perampanel

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End point title

Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of this Study: Assessment Based on Relationship With Plasma Levels of Perampanel

End point description

The ABNAS assessment measured 5 aspects of cognitive function such as fatigue, memory, concentration, motor speed, and reading. The assessment was a measure of subject-perceived cognitive effects of AEDs. This instrument was aimed at assessing subject perceived drug-related cognitive impairment. Total score ranged from 0-72. Higher scores indicate a worsening of these cognitive functions. Analysis for this OM was planned to be performed via Pharmacokinetic/Pharmacodynamic (PK/PD) modelling only if a graphical relationship between perampanel exposure and change from baseline in ABNAS could be discerned. All subjects who received perampanel who have seizure frequency, cognition, or AE data with documented dosing history. Here "number of subjects analyzed" signifies subjects who were evaluable for this outcome measure and 99999 signifies no discernible graphical relationship between plasma level of perampanel and change from baseline.

End point type

Secondary

End point timeframe

Baseline up to Week 23

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	148
Units: score on a scale
arithmetic mean (standard deviation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged 4 to 5 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

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End point title

Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged 4 to 5 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

End point description

CBCL for subjects with age 4-5 years is questionnaire to assess behavioral;emotional problems in children as reported by primary caregiver for following domains activities: emotionally reactive, anxious/depressed, withdrawn, somatic complaints, internalizing, attention problems, aggressive behavior, externalizing, sleep problems. CBCL total score ranged from 0 to 200,calculated by adding individual score of each domain. Higher scores greater problems in child behavior. Analysis for this OM was planned to be performed via PK/PD modelling only if graphical relationship between perampanel exposure; change from baseline in CBCL score (subjects aged 4 to 5 years) could be discerned. All subjects who received perampanel who have seizure frequency, cognition, or AE data with documented dosing history. Here "number of subjects analyzed": subjects who were evaluable for this OM and 99999 signifies no discernible graphical relationship between plasma level of perampanel; change from baseline.

End point type

Secondary

End point timeframe

Baseline up to Week 23

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	19
Units: score on a scale
arithmetic mean (standard deviation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged Greater Than [>] 5 to <12 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

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End point title

Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged Greater Than [>] 5 to <12 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

End point description

CBCL for subjects >5 -<12 years questionnaire to assess behavioral;emotional problems in children reported by primary caregiver for following domain activities: activity, social, school, total competence, anxious/depressed, withdrawn/depressed, somatic complaints, internalizing, rule-breaking behavior, aggressive behavior, externalizing, social problems, thought problems, attention problems.Total score for subjects:>5 -<12 years ranged: 0-240, calculated by adding individual score of each domain.Higher scores greater problems in behavior.Analysis performed via PK/PD modelling only if graphical relationship between perampanel exposure;change from baseline in CBCL score(aged >5 -<12 years) could discerned.All subjects received perampanel with seizure frequency,cognition,or AE data with documented dosing history. "number of subjects analyzed": subjects evaluable for this OM; 99999 signifies no discernible graphical relationship between plasma level of perampanel; change from baseline.

End point type

Secondary

End point timeframe

Baseline up to Week 23

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	115
Units: score on a scale
arithmetic mean (standard deviation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

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End point title

Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

End point description

Lafayette Grooved Pegboard Test (LGPT) measures visuomotor skills. It is manipulative dexterity test consist of metal matrix of 25 holes; randomly positioned slots.Subjects require to insert 10 grooved pegs into holes.Task needs to complete once for each hand; firstly, dominant hand and by non-dominant hand.Task is timed; scores are time taken for subject to complete all 10 pegs for each hand. If cannot be completed within 300 secs, 300 secs recorded for time.Longer time worsening of visuomotor skills.Analysis was planned to be performed via PK/PD modelling only if graphical relationship between perampanel exposure;change from baseline in Total Time to Complete LGPT Score for Non-dominant Hand could be discerned.All subjects who received perampanel who have seizure frequency,cognition,or AE data documented dosing history."number of subjects analyzed": subjects evaluable for this OM; 99999: no discernible graphical relationship between plasma level of perampanel; change from baseline.

End point type

Secondary

End point timeframe

Baseline up to Week 23

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	117
Units: seconds
arithmetic mean (standard deviation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Non-dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

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End point title

Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Non-dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 23

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	113
Units: seconds
arithmetic mean (standard deviation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Percentage of Subjects With Most Frequent Treatment Emergent Adverse Events (AEs) for Total Group of Subjects That Were Considered Related to Perampanel- Core Phase of This Study

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End point title

Percentage of Subjects With Most Frequent Treatment Emergent Adverse Events (AEs) for Total Group of Subjects That Were Considered Related to Perampanel- Core Phase of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline up to 23 weeks

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	180
Units: percentage of subjects
number (not applicable)
Irritability	12.8
Nasopharyngitis	14.7
Influenza	6.4
Pyrexia	9.0
Somnolence	13.5

No statistical analyses for this end point

Secondary: Change From Baseline in Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (n =140,30)	17.7 ( 18.96 )	28.6 ( 21.01 )
Change from Baseline at Week 23 (n=107,19)	-1.2 ( 12.77 )	3.3 ( 12.42 )
Change from Baseline at Week 52 (n=95,17)	-3.9 ( 16.91 )	-0.2 ( 14.67 )

No statistical analyses for this end point

Secondary: Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 1.5 to 5 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 1.5 to 5 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

The CBCL for subjects (age group 1.5 to 5 years) is a questionnaire to assess behavioral and emotional problems in children as reported by the primary caregiver for the following domains activities: emotionally reactive, anxious/depressed, withdrawn, somatic complaints, internalizing, attention problems, aggressive behavior, externalizing, sleep problems. CBCL total score for subjects (age group 1.5 to 5 years) ranged from 0 to 200, was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior. SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subjects analyzed" signifies subjects who were evaluable for this OM and '99999' indicates that standard deviation could not be estimated for single subject for the specified arm.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	24	2
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (n=24,2)	35.0 ( 28.30 )	54.0 ( 21.21 )
Change from Baseline at Week 23 (n=15,1)	-0.3 ( 14.71 )	-13.0 ( 99999 )
Change from Baseline at Week 52 (n=16,1)	-5.7 ( 14.36 )	-11.0 ( 99999 )

No statistical analyses for this end point

Secondary: Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 6 to 18 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 6 to 18 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

CBCL for subjects (age 6 to 18 years) questionnaire to assess behavioral and emotional problems in children as reported by primary caregiver for the following domains activities: activity, social, school, total competence, anxious/depressed, withdrawn/depressed, somatic complaints, internalizing, rule-breaking behavior, aggressive behavior, externalizing, social problems, thought problems, attention problems. Total score for subjects (age group 6 to 18 years) ranged from 0 to 240, calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior. SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subjects analyzed" signifies subjects who were evaluable for this OM.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	123	28
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (n=123,28)	33.3 ( 22.66 )	44.6 ( 26.16 )
Change from Baseline at Week 23 (n=96,18)	-0.6 ( 12.26 )	-2.2 ( 22.84 )
Change from Baseline at Week 52 (n=86,16)	-1.7 ( 14.51 )	-0.7 ( 16.36 )

No statistical analyses for this end point

Secondary: Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores for 8 Years and Under at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores for 8 Years and Under at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

LGPT test measured visuomotor skills. This test was a manipulative dexterity test that consisted of a metal matrix of 25 holes with randomly positioned slots. The subject was required to insert 10 grooved pegs into the holes. The task was completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task was timed and the scores were the time taken for the subject to complete all 10 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds were recorded for the time. An increase in score (longer time) indicated worsening of visuomotor skills. The time to complete test is presented as mean seconds plus/minus (+/-) SD. SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subject analyzed" signifies subject who were evaluable for this OM and CFB indicates change from baseline.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	51	10
Units: seconds
arithmetic mean (standard deviation)
Dominant Hand: Baseline (n=51,10)	196.4 ( 113.12 )	155.0 ( 108.10 )
Dominant Hand: CFB :Week 23 (n=36,3)	12.8 ( 49.37 )	-4.3 ( 3.79 )
Dominant Hand: CFB: Week 52 (n=28,5)	3.9 ( 50.50 )	13.4 ( 33.72 )
Non Dominant Hand: Baseline (n=50,9)	224.3 ( 108.19 )	169.6 ( 106.49 )
Non Dominant Hand: CFB Week 23 (n=36,3)	3.3 ( 39.59 )	-4.3 ( 14.98 )
Non Dominant Hand: CFB Week 52 (n=29,5)	2.6 ( 46.88 )	3.4 ( 29.35 )

No statistical analyses for this end point

Secondary: Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores Over 8 Years at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores Over 8 Years at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

The LGPT test measured visuomotor skills.This test was a manipulative dexterity test that consisted of a metal matrix of 25 holes with randomly positioned slots. The subject was required to insert 25 grooved pegs into the holes. The task was completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task was timed and the scores were the time taken for the subject to complete all 25 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds were recorded for the time. An increase in score (longer time) indicated worsening of visuomotor skills. The time to complete test is presented as mean seconds +/- SD. SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subjects analyzed" signifies subjects who were evaluable for this OM and CFB indicates change from baseline.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	63	11
Units: seconds
arithmetic mean (standard deviation)
Dominant Hand: Baseline (n=63,11)	189.8 ( 103.58 )	150.7 ( 99.68 )
Dominant Hand: CFB at Week 23 (n=50,9)	0.1 ( 21.77 )	-11.8 ( 35.05 )
Dominant Hand: CFB at Week 52 (n=44,7)	3.0 ( 21.24 )	-15.4 ( 30.43 )
Non Dominant Hand: Baseline (n=61,10)	197.4 ( 100.01 )	159.9 ( 84.66 )
Non Dominant Hand: CFB at Week 23 (n=49,8)	7.8 ( 36.03 )	-7.0 ( 21.98 )
Non Dominant Hand: CFB at Week 52 (n=42,6)	2.7 ( 23.75 )	-28.7 ( 36.15 )

No statistical analyses for this end point

Secondary: Change From Baseline in Height (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Height (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: centimeter (cm)
arithmetic mean (standard deviation)
Baseline (n=149,29)	126.65 ( 14.293 )	131.08 ( 13.311 )
Change from Baseline Week 23 (n=114,18)	2.57 ( 1.926 )	1.84 ( 1.111 )
Change from Baseline Week 52 (n=104,17)	5.97 ( 2.580 )	5.82 ( 2.544 )

No statistical analyses for this end point

Secondary: Change From Baseline in Weight (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Weight (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: kilogram (kg)
arithmetic mean (standard deviation)
Baseline (n=149,31)	28.09 ( 10.649 )	30.43 ( 11.299 )
Change from Baseline Week 23 (n=117,21)	1.86 ( 2.570 )	1.70 ( 3.149 )
Change from Baseline Week 52 (n=104,18)	3.75 ( 4.421 )	3.74 ( 4.204 )

No statistical analyses for this end point

Secondary: Change From Baseline in Thyrotropin Value (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Thyrotropin Value (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

Thyrotropin level was measured in milli-international units per liter (mIU/L). SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: mIU/L
arithmetic mean (standard deviation)
Baseline (n=146,30)	2.682 ( 1.5897 )	3.080 ( 2.2919 )
Change from Baseline Week 23 (n=104,17)	0.141 ( 1.0523 )	-0.519 ( 1.4828 )
Change from Baseline Week 52 (n=97,17)	0.112 ( 1.2559 )	-0.632 ( 1.5632 )

No statistical analyses for this end point

Secondary: Change From Baseline in Thyroxine, Free and Triiodothyronine, Free Values (Growth and Development Parameters) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Thyroxine, Free and Triiodothyronine, Free Values (Growth and Development Parameters) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: picomoles per liter (pmol/L)
arithmetic mean (standard deviation)
Thyroxine,free:Baseline (n=146,30)	15.29 ( 3.993 )	15.37 ( 2.160 )
Thyroxine,free:Change Week 23 (n=103,17)	-0.07 ( 4.107 )	-0.38 ( 2.088 )
Thyroxine,free:Change Week 52 (n=96,17)	0.10 ( 3.868 )	0.08 ( 2.968 )
Triiodothyronine,free:Baseline (n=146,30)	5.96 ( 1.061 )	6.10 ( 0.812 )
Triiodothyronine,free: Change Week 23 (n=105,18)	0.06 ( 0.915 )	-0.16 ( 0.699 )
Triiodothyronine,free:Change Week 52 (n= 96,17)	0.04 ( 0.987 )	-0.04 ( 1.107 )

No statistical analyses for this end point

Secondary: Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Values (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

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End point title

Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Values (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: nanomoles per liter (nmol/L)
arithmetic mean (standard deviation)
Baseline (n=144,31)	24.2 ( 14.83 )	25.9 ( 13.91 )
Change from Baseline Week 23 (n=107,18)	1.6 ( 8.96 )	0.6 ( 7.25 )
Change from Baseline Week 52 (n=96,16)	6.5 ( 9.01 )	5.1 ( 8.02 )

No statistical analyses for this end point

Secondary: Percentage of Subjects With Change From Baseline in Markedly Abnormal Encephalogram (EEG) Parameter Values During Awake and Sleep State for Total Group of Subject: Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Change From Baseline in Markedly Abnormal Encephalogram (EEG) Parameter Values During Awake and Sleep State for Total Group of Subject: Core Phase and Extension Phase A of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline up to 52 weeks

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	180
Units: percentage of subjects	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Any Treatment-emergent Reports of Suicidal Ideation and Behavior Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Any Treatment-emergent Reports of Suicidal Ideation and Behavior Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)- Core Phase and Extension Phase A of This Study

End point description

C-SSRS: interview-based instrument to systematically assess suicidal ideation (SI); suicidal behavior, whether: completed suicide,suicide attempt (response of "yes" on "actual attempt"),preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior","aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead","non-specific active suicidal thoughts","active SI with methods without intent to act or some intent to act,without specific plan or with specific plan and intent), any self-injurious behavior with no suicidal intent ("yes" on "has subject engaged in non-suicidal self-injurious behavior"). Percentage of subjects with >=1 positive behavior/ideations,suicidality were reported.C-SSRS performed: >=6 years at time of consent. SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment. "number of subjects analyzed" signifies subjects who were evaluable for this OM.

End point type

Secondary

End point timeframe

Up to 52 weeks

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	122	27
Units: percentage of subjects
number (not applicable)
Subjects with >=1 Positive Behavior	0.8	0
Subjects with >= Positive Ideations	1.6	7.4
Suicidality	1.6	7.4

No statistical analyses for this end point

Secondary: Number of Encephalogram (EEG) Abnormalities During Awake and Sleep State for Total Group of Subjects: Core Phase and Extension Phase A of This Study

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End point title

Number of Encephalogram (EEG) Abnormalities During Awake and Sleep State for Total Group of Subjects: Core Phase and Extension Phase A of This Study

End point description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Baseline up to 52 weeks

End point values	Perampanel 0.5 mg/mL: All Subjects
Number of subjects analysed	180
Units: EEG abnormality	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Shift From Baseline in Suicidal Ideation and Behaviors Assessed Using C-SSRS Scores to Extension Phase A (Week 52) of This Study

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End point title

Percentage of Subjects With Shift From Baseline in Suicidal Ideation and Behaviors Assessed Using C-SSRS Scores to Extension Phase A (Week 52) of This Study

End point description

C-SSRS: interview-based instrument to systematically assess SI and suicidal behavior, to assess whether subject experienced any of the following: completed suicide, suicide attempt (response of "yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active SI with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any self-injurious behavior with no suicidal intent ("yes" on "has subject engaged in non-suicidal self-injurious behavior"). "w/" refers to "with", "W" refers to "Week" and "&" refers to "and". SAS included all subject who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Here "number of subject analyzed" signifies subject who were evaluable for this measure.

End point type

Secondary

End point timeframe

Up to 52 weeks

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	122	27
Units: percentage of subjects
number (not applicable)
No Ideation(Baseline) to No Ideation(Week 52)	96.6	88.9
Wish to be Dead(Baseline) to No ideation(Week 52)	0.9	3.7
Active w/ Method(Baseline) to No Ideation(Week 52)	0.9	0
No Ideation(Baseline)to Active Nonspecific(Week52)	0	3.7
No Ideation(Baseline) to Active w/ Method(Week 52	0.9	3.7
No Ideation(Baseline)to Active w/ Intent&Plan(W52)	0.9	0

No statistical analyses for this end point

Secondary: Median Percent Change in Seizure Frequency Per 28 Days During the Treatment Phase Relative to the Pretreatment Phase (Baseline)- Core Phase and Extension Phase A of This Study

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End point title

Median Percent Change in Seizure Frequency Per 28 Days During the Treatment Phase Relative to the Pretreatment Phase (Baseline)- Core Phase and Extension Phase A of This Study

End point description

Seizure frequency was based on number of seizures per 28 days, calculated as number of seizures over entire time interval divided by number of days in interval and multiplied by 28. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with secondary generalization (SG). Data for this measure has been reported for 13 week time periods as per age groups. Full Analysis Set (FAS) included subjects who received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

End point type

Secondary

End point timeframe

Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52

End point values	Perampanel 0.5 mg/mL: 4 to <7 Years	Perampanel 0.5 mg/mL: 7 to <12 Years
Number of subjects analysed	46	134
Units: percent change
median (full range (min-max))
POS Seizures:Weeks 1-13 (n=40,108)	-47.99 (-100.0 to 79.1)	-40.97 (-100.0 to 549.0)
POS Seizures:Weeks 14-26 (n=38,91)	-38.93 (-100.0 to 175.0)	-50.77 (-100.0 to 360.5)
POS Seizures:Weeks 27-39 (n=32,82)	-52.53 (-100.0 to 344.2)	-67.30 (-100.0 to 387.9)
POS Seizures:Weeks 40-52 (n=31,77)	-58.92 (-100.0 to 482.7)	-70.33 (-100.0 to 436.3)
PGTC Seizures:Weeks 1-13 (n=3,19)	-100.00 (-100.0 to 2115.9)	-70.33 (-100.0 to 6783.5)
PGTC Seizures:Weeks 14-26 (n=3,15)	-100.00 (-100.0 to -7.7)	-70.70 (-100.0 to 879.1)
PGTC Seizures:Weeks 27-39 (n=2,13)	-80.77 (-100.0 to -61.5)	-65.43 (-100.0 to 315.4)
PGTC Seizures:Weeks 40-52 (n=2,11)	-100.00 (-100.0 to -100.0)	-96.54 (-100.0 to 658.4)

No statistical analyses for this end point

Secondary: Percentage of Subjects Based on 25% Responder Rate- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects Based on 25% Responder Rate- Core Phase and Extension Phase A of This Study

End point description

A 25% responder was a subject who experienced a 25% or greater reduction in seizure frequency per 28 days from baseline. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this OM has been reported for 13 week time periods as per age groups. FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

End point type

Secondary

End point timeframe

Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52

End point values	Perampanel 0.5 mg/mL: 4 to <7 Years	Perampanel 0.5 mg/mL: 7 to <12 Years
Number of subjects analysed	46	134
Units: percentage of subjects
number (not applicable)
Total POS Seizures: Weeks 1-13	67.5	61.1
Total POS Seizures: Weeks 14-26	57.9	71.4
Total POS Seizures: Weeks 27-39	71.9	78.0
Total POS Seizures: Weeks 40-52	71.0	81.8
PGTC Seizures: Weeks 1-13	66.7	73.7
PGTC Seizures: Weeks 14-26	66.7	73.3
PGTC Seizures: Weeks 27-39	100.0	69.2
PGTC Seizures: Weeks 40-52	100.0	63.6

No statistical analyses for this end point

Secondary: Percentage of Subjects Based on 50% Responder Rate- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects Based on 50% Responder Rate- Core Phase and Extension Phase A of This Study

End point description

A 50% responder was a subject who experienced a 50% or greater reduction in seizure frequency per 28 days from baseline. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this OM has been reported for 13 week time periods as per age groups. FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

End point type

Secondary

End point timeframe

Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52

End point values	Perampanel 0.5 mg/mL: 4 to <7 Years	Perampanel 0.5 mg/mL: 7 to <12 Years
Number of subjects analysed	46	134
Units: percentage of subjects
number (not applicable)
Total POS Seizures: Weeks 1-13	47.5	45.4
Total POS Seizures: Weeks 14-26	44.7	50.5
Total POS Seizures: Weeks 27-39	53.1	65.9
Total POS Seizures: Weeks 40-52	61.3	62.3
PGTC Seizures: Weeks 1-13	66.7	57.9
PGTC Seizures: Weeks 14-26	66.7	60.0
PGTC Seizures: Weeks 27-39	100.0	61.5
PGTC Seizures: Weeks 40-52	100.0	54.5

No statistical analyses for this end point

Secondary: Percentage of Subjects Based on 75% Responder Rate- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects Based on 75% Responder Rate- Core Phase and Extension Phase A of This Study

End point description

A 75% responder was a subject who experienced a 75% or greater reduction in seizure frequency per 28 days from baseline. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this OM has been reported for 13 week time periods as per age groups. FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

End point type

Secondary

End point timeframe

Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52

End point values	Perampanel 0.5 mg/mL: 4 to <7 Years	Perampanel 0.5 mg/mL: 7 to <12 Years
Number of subjects analysed	46	134
Units: percentage of subjects
number (not applicable)
Total POS Seizures: Weeks 1-13	17.5	25.0
Total POS Seizures: Weeks 14-26	18.4	34.1
Total POS Seizures: Weeks 27-39	31.3	46.3
Total POS Seizures: Weeks 40-52	38.7	41.6
PGTC Seizures: Weeks 1-13	66.7	47.4
PGTC Seizures: Weeks 14-26	66.7	46.7
PGTC Seizures: Weeks 27-39	50.0	46.2
PGTC Seizures: Weeks 40-52	100.0	54.5

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Were Seizure-free- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects Who Were Seizure-free- Core Phase and Extension Phase A of This Study

End point description

Subjects were considered seizure free if subjects completed a 13-week time period and were seizure-free for that entire time period. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this OM has been reported for 13 week time periods as per age groups. FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

End point type

Secondary

End point timeframe

Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52

End point values	Perampanel 0.5 mg/mL: 4 to <7 Years	Perampanel 0.5 mg/mL: 7 to <12 Years
Number of subjects analysed	46	134
Units: percentage of subjects
number (not applicable)
Total POS Seizures: Weeks 1-13	7.9	9.9
Total POS Seizures: Weeks 14-26	9.4	15.9
Total POS Seizures: Weeks 27-39	12.9	24.7
Total POS Seizures: Weeks 40-52	15.0	20.8
PGTC Seizures: Weeks 1-13	66.7	40.0
PGTC Seizures: Weeks 14-26	50.0	46.2
PGTC Seizures: Weeks 27-39	50.0	45.5
PGTC Seizures: Weeks 40-52	100.0	57.1

No statistical analyses for this end point

Secondary: Percentage of Subjects With Clinical Global Impression of Change Scores (CGIC)- Core Phase and Extension Phase A of This Study

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End point title

Percentage of Subjects With Clinical Global Impression of Change Scores (CGIC)- Core Phase and Extension Phase A of This Study

End point description

Assessment of disease severity utilized the CGIC scale at end of treatment to evaluate subject's change in disease status from baseline. The CGIC is a 7-point scale that measures a physician's global impression of a subject's clinical condition. Scale ranged from 1 to 7 with lower score indicated improvement (1=very much improved, 2=much improved, 3=minimally improved), higher score indicated worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicated no change. FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

End point type

Secondary

End point timeframe

Baseline, Week 23, Week 52

End point values	Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Number of subjects analysed	149	31
Units: percentage of subjects
number (not applicable)
Week 23: Very much improved	11.5	8.7
Week 23: Much improved	31.1	26.1
Week 23: Minimally improved	38.5	26.1
Week 23: No change	14.8	26.1
Week 23: Minimally worse	3.3	13.0
Week 23: Much worse	0.8	0
Week 52: Very much improved	14.4	5.9
Week 52: Much improved	39.4	41.2
Week 52: Minimally improved	35.6	29.4
Week 52: No change	7.7	17.6
Week 52: Minimally worse	1.9	5.9
Week 52: Much worse	1.0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From baseline up to approximately 5 years

Adverse event reporting additional description

SAS included all subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Perampanel 0.5 mg/mL: POS

Reporting group description

Core Phase: Subjects with POS received perampanel 0.5 mg/mL oral suspension titrated beyond 8 mg/day up to 12 mg/day, if 8 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are not taking any EIAED), or titrated beyond 12 mg/day up to 16 mg/day, if 12 mg/day was tolerable and were deemed likely to be benefitted by higher dose (for subjects who are taking any EIAED). Dose titration- up to 11 weeks to identify each subject's optimum dose. Subjects then continued to take perampanel once daily at optimal dose level as a maintenance dose for up to 12 weeks. Extension Phase A: Subjects who completed Core Phase, entered Extension Phase A, and continued with their optimal perampanel dose from Core Phase for up to 29 weeks. Total duration of treatment for Core Phase and Extension Phase A was up to 52 weeks.

Reporting group title

Extension B: Perampanel 0.5 mg/mL: PGTC Seizures

Reporting group description

Reporting group title

Extension B: Perampanel 0.5 mg/mL: POS

Reporting group description

Reporting group title

Perampanel 0.5 mg/mL: PGTC Seizures

Reporting group description

Serious adverse events	Perampanel 0.5 mg/mL: POS	Extension B: Perampanel 0.5 mg/mL: PGTC Seizures	Extension B: Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Total subjects affected by serious adverse events
subjects affected / exposed	29 / 149 (19.46%)	0 / 1 (0.00%)	8 / 41 (19.51%)	7 / 31 (22.58%)
number of deaths (all causes)	1	0	0	0
number of deaths resulting from adverse events	1	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of testis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haemangioma
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Subgaleal haematoma
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dysarthria
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ataxia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Focal dyscognitive seizures
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rasmussen encephalitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Petit mal epilepsy
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure cluster
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Gait disturbance
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Dental caries
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis erosive
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract inflammation
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Aggression
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Disruptive mood dysregulation disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hallucination, visual
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Epiphysiolysis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	5 / 41 (12.20%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection pseudomonal
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral myocarditis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Perampanel 0.5 mg/mL: POS	Extension B: Perampanel 0.5 mg/mL: PGTC Seizures	Extension B: Perampanel 0.5 mg/mL: POS	Perampanel 0.5 mg/mL: PGTC Seizures
Total subjects affected by non serious adverse events
subjects affected / exposed	135 / 149 (90.60%)	1 / 1 (100.00%)	34 / 41 (82.93%)	25 / 31 (80.65%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Vascular disorders
Peripheral coldness
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Subgaleal haematoma
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	2
Crying
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Fatigue
subjects affected / exposed	9 / 149 (6.04%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	11	0	0	2
Gait disturbance
subjects affected / exposed	7 / 149 (4.70%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	7	0	0	0
Influenza like illness
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Pain
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0	0
Pyrexia
subjects affected / exposed	25 / 149 (16.78%)	0 / 1 (0.00%)	4 / 41 (9.76%)	4 / 31 (12.90%)
occurrences all number	39	0	4	6
Medical device pain
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Screaming
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Immune system disorders
Rubber sensitivity
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Seasonal allergy
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	5	0	0	7
Asthma
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	2	0	1	0
Epistaxis
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	6	0	0	3
Lower respiratory tract congestion
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Increased upper airway secretion
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Oropharyngeal pain
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	5	0	1	0
Nasal congestion
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	1	0	0	2
Productive cough
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Rhinorrhoea
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	4	0	0	2
Rhinitis allergic
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Upper respiratory tract inflammation
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	3 / 41 (7.32%)	0 / 31 (0.00%)
occurrences all number	4	0	3	0
Respiratory disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Sleep apnoea syndrome
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Upper airway obstruction
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Bronchitis chronic
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Increased bronchial secretion
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Pneumonia aspiration
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Psychiatric disorders
Abnormal behaviour
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Adjustment disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Affect lability
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Agitation
subjects affected / exposed	7 / 149 (4.70%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	11	0	0	2
Aggression
subjects affected / exposed	15 / 149 (10.07%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	22	0	0	2
Anger
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0	0
Anxiety
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	5	0	0	2
Attention deficit/hyperactivity disorder
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0	0
Defiant behaviour
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Bradyphrenia
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	6	0	0	0
Dysphemia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Dysphoria
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Enuresis
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0	0
Euphoric mood
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Hypervigilance
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Insomnia
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	2 / 41 (4.88%)	1 / 31 (3.23%)
occurrences all number	5	0	2	3
Irritability
subjects affected / exposed	19 / 149 (12.75%)	0 / 1 (0.00%)	1 / 41 (2.44%)	5 / 31 (16.13%)
occurrences all number	20	0	1	5
Learning disability
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Mood altered
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Middle insomnia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Nightmare
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Oppositional defiant disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Negativism
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Personality change
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Restlessness
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	2	0	1	0
Somnambulism
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Suicidal ideation
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	2
Sleep disorder
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0	0
Tic
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Distractibility
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Initial insomnia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Intentional self-injury
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Investigations
Body temperature increased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Urine output decreased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	2	0	1	0
Weight decreased
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	3	0	0	1
Weight increased
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	6	0	0	2
Alanine aminotransferase increased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Blood pressure systolic increased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Crystal urine present
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Blood uric acid increased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Eosinophil count increased
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Tri-iodothyronine free increased
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
White blood cells urine positive
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Ammonia increased
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Blast cell count increased
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	2 / 41 (4.88%)	0 / 31 (0.00%)
occurrences all number	0	0	3	0
Neutrophil count decreased
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Animal bite
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Arthropod sting
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Contusion
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	1 / 41 (2.44%)	1 / 31 (3.23%)
occurrences all number	6	0	1	1
Eye contusion
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Eye injury
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Fall
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	2	0	0	3
Head injury
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	2	0
Foot fracture
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Forearm fracture
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Laceration
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	3	0	0	3
Joint injury
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Ligament sprain
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	2	0	1	0
Limb injury
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Mallet finger
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Nail avulsion
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Scar
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Seroma
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Skin abrasion
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	5	0	1	0
Wound
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Thermal burn
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Wrist fracture
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Clavicle fracture
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Joint dislocation
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Heat stroke
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Stoma site hypergranulation
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Traumatic haematoma
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Arthropod bite
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Femur fracture
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Incision site erosion
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Lip injury
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Amnesia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Ataxia
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	10	0	0	2
Atonic seizures
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Balance disorder
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	8	0	0	3
Cerebral haematoma
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Coordination abnormal
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Clumsiness
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Cognitive disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Dizziness
subjects affected / exposed	19 / 149 (12.75%)	0 / 1 (0.00%)	0 / 41 (0.00%)	5 / 31 (16.13%)
occurrences all number	24	0	0	8
Disturbance in attention
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	5	0	0	1
Drooling
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0	0
Dysarthria
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	2	0	0	2
Dyslexia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Focal dyscognitive seizures
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Dysstasia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Headache
subjects affected / exposed	10 / 149 (6.71%)	0 / 1 (0.00%)	1 / 41 (2.44%)	5 / 31 (16.13%)
occurrences all number	18	0	1	7
Hypotonia
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Lethargy
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Memory impairment
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	3	0	0	3
Motor dysfunction
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	2	0	0	1
Nystagmus
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Persistent postural-perceptual dizziness
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Petit mal epilepsy
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	2	0	0	1
Postictal state
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Psychomotor hyperactivity
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	6	0	0	3
Psychomotor skills impaired
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Sedation
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	3
Seizure
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	9	0	0	4
Somnolence
subjects affected / exposed	43 / 149 (28.86%)	0 / 1 (0.00%)	1 / 41 (2.44%)	5 / 31 (16.13%)
occurrences all number	49	0	1	9
Status epilepticus
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Epilepsy
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Hippocampal sclerosis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Migraine
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Poor quality sleep
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Seizure cluster
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	2	0
Simple partial seizures
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Tremor
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Myoclonus
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Fine motor skill dysfunction
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Increased tendency to bruise
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Thrombocytopenia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Iron deficiency anaemia
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Macrocytosis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Neutropenia
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Tympanic membrane perforation
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Vertigo
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	2	0	0	3
Eye disorders
Conjunctivitis allergic
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	4 / 41 (9.76%)	0 / 31 (0.00%)
occurrences all number	2	0	5	0
Corneal disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Diplopia
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	4	0	0	2
Mydriasis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Vision blurred
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Conjunctival hyperaemia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Keratitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	2 / 41 (4.88%)	0 / 31 (0.00%)
occurrences all number	1	0	2	0
Strabismus
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Eye discharge
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Eyelid oedema
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Lagophthalmos
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Abdominal pain
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	8	0	0	2
Abdominal pain upper
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Constipation
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	2 / 41 (4.88%)	3 / 31 (9.68%)
occurrences all number	5	0	3	5
Anal incontinence
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Diarrhoea
subjects affected / exposed	9 / 149 (6.04%)	0 / 1 (0.00%)	3 / 41 (7.32%)	3 / 31 (9.68%)
occurrences all number	13	0	6	5
Dry mouth
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Dysphagia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	2	0	1	0
Enteritis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Erosive oesophagitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Haematemesis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Nausea
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	1 / 41 (2.44%)	1 / 31 (3.23%)
occurrences all number	4	0	1	1
Odynophagia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Salivary hypersecretion
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	6	0	0	0
Stomatitis
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0	0
Toothache
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	3	0	0	1
Vomiting
subjects affected / exposed	20 / 149 (13.42%)	0 / 1 (0.00%)	5 / 41 (12.20%)	5 / 31 (16.13%)
occurrences all number	23	0	13	6
Dental caries
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	2 / 41 (4.88%)	0 / 31 (0.00%)
occurrences all number	1	0	2	0
Functional gastrointestinal disorder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Ranula
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Enterocolitis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Gastritis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Gastrointestinal motility disorder
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Gingival hypertrophy
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Haemorrhoids
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Tooth discolouration
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Hepatobiliary disorders
Drug-induced liver injury
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	3	0	0	1
Alopecia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Dermatitis contact
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	4	0	1	0
Dermatitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	3 / 41 (7.32%)	0 / 31 (0.00%)
occurrences all number	1	0	3	0
Drug eruption
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Dermatitis diaper
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Eczema
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	2 / 41 (4.88%)	1 / 31 (3.23%)
occurrences all number	2	0	2	1
Mechanical urticaria
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Erythema
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Rash
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	2 / 41 (4.88%)	1 / 31 (3.23%)
occurrences all number	13	0	2	1
Miliaria
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0	0
Rash erythematous
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Rash papular
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Rash morbilliform
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Urticaria
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0	0
Skin hyperpigmentation
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Angioedema
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Dermatitis atopic
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Rash generalised
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Rash maculo-papular
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Skin erosion
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Blister
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Decubitus ulcer
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Yellow skin
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Nail dystrophy
subjects affected / exposed	0 / 149 (0.00%)	1 / 1 (100.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	0	1	0	0
Renal and urinary disorders
Urinary incontinence
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	4	0	0	2
Polyuria
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Haematuria
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Hypertonic bladder
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Pollakiuria
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Proteinuria
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Vesicoureteric reflux
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Precocious puberty
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Kyphosis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Muscle spasms
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Muscle rigidity
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	2
Pain in extremity
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Periosteal haematoma
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Arthritis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Infections and infestations
Acute sinusitis
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0	0
Beta haemolytic streptococcal infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Bronchitis
subjects affected / exposed	10 / 149 (6.71%)	0 / 1 (0.00%)	4 / 41 (9.76%)	0 / 31 (0.00%)
occurrences all number	11	0	6	0
Conjunctivitis
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	4 / 41 (9.76%)	1 / 31 (3.23%)
occurrences all number	5	0	5	1
Ear infection
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	2 / 31 (6.45%)
occurrences all number	3	0	0	2
Enterocolitis viral
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Fungal skin infection
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Fungal infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Gastroenteritis
subjects affected / exposed	11 / 149 (7.38%)	1 / 1 (100.00%)	1 / 41 (2.44%)	2 / 31 (6.45%)
occurrences all number	14	1	1	2
Hordeolum
subjects affected / exposed	3 / 149 (2.01%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0	0
Influenza
subjects affected / exposed	20 / 149 (13.42%)	0 / 1 (0.00%)	6 / 41 (14.63%)	0 / 31 (0.00%)
occurrences all number	23	0	6	0
Lymphangitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Nasopharyngitis
subjects affected / exposed	40 / 149 (26.85%)	0 / 1 (0.00%)	14 / 41 (34.15%)	3 / 31 (9.68%)
occurrences all number	73	0	25	4
Oral herpes
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Otitis externa
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Otitis media
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Otitis media acute
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Pharyngitis
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	2 / 41 (4.88%)	0 / 31 (0.00%)
occurrences all number	6	0	2	0
Paronychia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Pharyngitis streptococcal
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	3	0	0	1
Pneumonia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	6 / 41 (14.63%)	0 / 31 (0.00%)
occurrences all number	1	0	8	0
Respiratory tract infection
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0	0
Respiratory tract infection viral
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Sinusitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	1
Rhinitis
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	0 / 41 (0.00%)	3 / 31 (9.68%)
occurrences all number	5	0	0	4
Streptococcal infection
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	3 / 41 (7.32%)	0 / 31 (0.00%)
occurrences all number	1	0	4	0
Tonsillitis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	1 / 31 (3.23%)
occurrences all number	2	0	1	1
Upper respiratory tract infection
subjects affected / exposed	15 / 149 (10.07%)	0 / 1 (0.00%)	3 / 41 (7.32%)	3 / 31 (9.68%)
occurrences all number	17	0	6	3
Urinary tract infection
subjects affected / exposed	5 / 149 (3.36%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	6	0	0	0
Viral infection
subjects affected / exposed	4 / 149 (2.68%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	6	0	1	0
Viral rash
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	0	2
Croup infectious
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Gastroenteritis viral
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0	0
Herpes zoster
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Impetigo
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Oral fungal infection
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Perianal streptococcal infection
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Tinea pedis
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Varicella
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	2 / 41 (4.88%)	0 / 31 (0.00%)
occurrences all number	1	0	2	0
Corona virus infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Erythema infectiosum
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Folliculitis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Lower respiratory tract infection
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	2 / 41 (4.88%)	0 / 31 (0.00%)
occurrences all number	0	0	2	0
Pneumonia mycoplasmal
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Pyelonephritis acute
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Respiratory syncytial virus bronchitis
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 149 (1.34%)	0 / 1 (0.00%)	0 / 41 (0.00%)	4 / 31 (12.90%)
occurrences all number	2	0	0	4
Increased appetite
subjects affected / exposed	6 / 149 (4.03%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	6	0	0	1
Hyperuricaemia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Polydipsia
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	0 / 41 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	0	1
Dehydration
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Hypoglycaemia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Hyponatraemia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	0 / 41 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0	0
Hypophosphataemia
subjects affected / exposed	1 / 149 (0.67%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	1	0	1	0
Hypokalaemia
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0
Vitamin D deficiency
subjects affected / exposed	0 / 149 (0.00%)	0 / 1 (0.00%)	1 / 41 (2.44%)	0 / 31 (0.00%)
occurrences all number	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

20 Apr 2017

Amendment 01: Added that the Titration Period is a fixed duration of 11 weeks and subjects will remain on their optimum dose once it is achieved during this period. Separated the Titration Period dosing schedule into separate presentations for Global sites and Japan sites. Increased the time prior to Visit 2 that subjects must meet the prior seizure criterion from 4 to 12 weeks. Increased the number of approved antiepileptic drug (AEDs) subjects may currently be receiving from 2 to 3. Added exclusion criterion for cannabinoids. Added exclusion of subjects with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Added emphasis that efforts should be made to perform all clinical laboratory and screening tests on the scheduled day, or as close as possible to that day, within 4 week period prior Visit 2.Added emphasis that efforts should be made to perform all clinical laboratory and screening tests on the scheduled day, or as close as possible to that day, within 4 week period prior Visit 2. Added mandatory blood collection for pharmacokinetic (PK) assessment. Revised study visit window to ±7 days of the scheduled visit. Grammatical, typographical, and formatting changes were also made.

19 Oct 2017

Amendment 02: Revised the Pretreatment Screening/Baseline Period (outside of Japan) to allow subjects to enrol sooner after a qualifying seizure, while maintaining the 4 weeks ±3 days required in Japan. Added that the study period durations were “up to” the specified nominal times. Added that analyses for regional submissions may be performed during the course of the study. Revised the sample size to state “at least” 160 subjects “(with up to 40 subjects with PGTC and the balance with POS)”. Added that each study visit is based on the actual prior visit (eg, Visit 3 is completed 2 weeks ±3 days of Visit 2, Visit 4 is completed 3 weeks ±3 days of Visit 3, etc). Revised study visit window during the Extension Phase back to ±6 days of the scheduled visit for Visits 10 through 12 (as per the original protocol). Grammatical, typographical, and formatting changes were also made.

19 Jan 2018

Amendment 03: Clarified, in the text, that the Followup Visit would be conducted at 4 weeks ± 7 days after the last dose of study drug for all subjects, except for subjects entering into Extension A. Clarified, in the text, that the follow-up period of Extension A was only for subjects not entering into Extension B and that Extension B will occur in Japan only. Clarified, in the text, that a follow-up period of Extension B, would include a Follow-up visit at 4 weeks ± 7 days after the Discontinuation Visit, and would occur for subjects who discontinue or who choose not to switch to the commercial product. Clarified, in the text, that subjects in all countries can enroll in Extension A. Clarified that the study visit window during Extension B is ±6 days of the scheduled visit. Clarified that the initial assessment of Extension B was performed at the final visit of Extension A Maintenance period (ie, Visit 12). Grammatical, typographical, and formatting changes were also made.

13 Jul 2018

Amendment 04: Clarified, in the text, that the Pretreatment Phase consists of a Screening/Baseline period. Clarified, in the text, the approximate total study duration. Clarified, in the text, that subjects in Japan and and in countries where an extended access program (EAP) cannot be implemented can enroll in Extension B. Specified criteria for participation in Extension B for subjects in countries where an EAP cannot be implemented. Clarified the CGI objective (CGIS is the baseline assessment and CGIC is the postbaseline assessment of the CGI). Grammatical, typographical, and formatting changes were also made.

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Subjects - Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Subjects - Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Subjects - Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Subjects - Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Abnormal Vital Sign Values for Total Group of Subjects- Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Abnormal Vital Sign Values for Total Group of Subjects- Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Subjects - Core Phase and Extension Phase A of This Study

Primary: Percentage of Subjects With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Subjects - Core Phase and Extension Phase A of This Study

Secondary: Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL)

Secondary: Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL)

Secondary: Overall Responder Probability For Non-Asian Subjects With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

Secondary: Overall Responder Probability For Non-Asian Subjects With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

Secondary: Overall Responder Probability For Subjects With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

Secondary: Overall Responder Probability For Subjects With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

Secondary: Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

Secondary: Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

Secondary: Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of this Study: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of this Study: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged 4 to 5 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged 4 to 5 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged Greater Than [>] 5 to <12 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Subjects Aged Greater Than [>] 5 to <12 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Non-dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Non-dominant Hand in Core Phase of This Study for All Subjects Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel

Secondary: Percentage of Subjects With Most Frequent Treatment Emergent Adverse Events (AEs) for Total Group of Subjects That Were Considered Related to Perampanel- Core Phase of This Study

Secondary: Percentage of Subjects With Most Frequent Treatment Emergent Adverse Events (AEs) for Total Group of Subjects That Were Considered Related to Perampanel- Core Phase of This Study

Secondary: Change From Baseline in Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 1.5 to 5 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 1.5 to 5 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 6 to 18 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 6 to 18 Years) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores for 8 Years and Under at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores for 8 Years and Under at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores Over 8 Years at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores Over 8 Years at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Height (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Height (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Weight (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Weight (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Thyrotropin Value (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Thyrotropin Value (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Thyroxine, Free and Triiodothyronine, Free Values (Growth and Development Parameters) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Thyroxine, Free and Triiodothyronine, Free Values (Growth and Development Parameters) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Values (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Values (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study

Secondary: Percentage of Subjects With Change From Baseline in Markedly Abnormal Encephalogram (EEG) Parameter Values During Awake and Sleep State for Total Group of Subject: Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects With Change From Baseline in Markedly Abnormal Encephalogram (EEG) Parameter Values During Awake and Sleep State for Total Group of Subject: Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects With Any Treatment-emergent Reports of Suicidal Ideation and Behavior Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects With Any Treatment-emergent Reports of Suicidal Ideation and Behavior Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)- Core Phase and Extension Phase A of This Study

Secondary: Number of Encephalogram (EEG) Abnormalities During Awake and Sleep State for Total Group of Subjects: Core Phase and Extension Phase A of This Study

Secondary: Number of Encephalogram (EEG) Abnormalities During Awake and Sleep State for Total Group of Subjects: Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects With Shift From Baseline in Suicidal Ideation and Behaviors Assessed Using C-SSRS Scores to Extension Phase A (Week 52) of This Study

Secondary: Percentage of Subjects With Shift From Baseline in Suicidal Ideation and Behaviors Assessed Using C-SSRS Scores to Extension Phase A (Week 52) of This Study

Secondary: Median Percent Change in Seizure Frequency Per 28 Days During the Treatment Phase Relative to the Pretreatment Phase (Baseline)- Core Phase and Extension Phase A of This Study

Secondary: Median Percent Change in Seizure Frequency Per 28 Days During the Treatment Phase Relative to the Pretreatment Phase (Baseline)- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Based on 25% Responder Rate- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Based on 25% Responder Rate- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Based on 50% Responder Rate- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Based on 50% Responder Rate- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Based on 75% Responder Rate- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Based on 75% Responder Rate- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Who Were Seizure-free- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects Who Were Seizure-free- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects With Clinical Global Impression of Change Scores (CGIC)- Core Phase and Extension Phase A of This Study

Secondary: Percentage of Subjects With Clinical Global Impression of Change Scores (CGIC)- Core Phase and Extension Phase A of This Study

Adverse events

Adverse events

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