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Clinical Trial Results:
An Open-label Pilot Study With an Extension Phase to Evaluate the Pharmacokinetics, and to Generate Preliminary Safety, Tolerability, and Efficacy of Perampanel (E2007) Oral Suspension When Given as an Adjunctive Therapy in Pediatric Subjects From 2 to Less Than 12 Years of Age With Epilepsy

Summary
EudraCT number	2011-001105-28
Trial protocol	Outside EU/EEA
Global end of trial date	13 Feb 2015

Results information
Results version number	v2(current)
This version publication date	07 Dec 2016
First version publication date	07 Aug 2016
Other versions	v1
Version creation reason	Correction of full data set Correction of data

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-G000-232

ISRCTN number

US NCT number

NCT01527006

WHO universal trial number (UTN)

Sponsor organisation name

Eisai Medical Research Inc.

Sponsor organisation address

155 Tice Boulevard, Woodcliff Lake, United States, 07677

Public contact

Eisai Medical Information, Eisai Inc., 888 274-2378, esi_medinfo@eisai.com

Scientific contact

Eisai Medical Information, Eisai Inc., 888 274-2378, esi_medinfo@eisai.com

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?

Analysis stage

Final

Date of interim/final analysis

19 Mar 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Feb 2015

Was the trial ended prematurely?

Main objective of the trial

To evaluate the pharmacokinetics (PK) of perampanel following oral suspension administration given as an adjunctive therapy in pediatric subjects from 2 to less than 12 years old with epilepsy

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Jan 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 50

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Of the 63 participants who were screened, 13 participants were screen failures and 50 participants were eligible to continue in the Core Study. Of the 42 subjects who completed the Core Study, 41 subjects continued into the Extension Phase.

Period 1 title

Core Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort ( ≥ 2 to < 7 years of age) - For Core Study

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

E2007

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Cohort ( ≥ 7 to < 12 years of age) - For Core Study

Arm description

Arm type

Experimental

Investigational medicinal product name

Perampanel

Investigational medicinal product code

E2007

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Started	22	28
Completed	20	22
Not completed	2	6
Adverse event, serious fatal	-	2
Participant choice	1	-
Not specified	-	2
Withdrawal by participant	-	1
Inadequate therapeutic effect	1	-
Lost to follow-up	-	1

Baseline characteristics

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Reporting group title

Cohort ( ≥ 2 to < 7 years of age) - For Core Study

Reporting group description

Reporting group title

Cohort ( ≥ 7 to < 12 years of age) - For Core Study

Reporting group description

Reporting group values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study	Total
Number of subjects	22	28	50
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
Units: years
median (full range (min-max))	5 (2 to 6)	9 (7 to 11)	-
Gender categorical
Units: Subjects
Female	7	9	16
Male	15	19	34

End points

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Reporting group title

Cohort ( ≥ 2 to < 7 years of age) - For Core Study

Reporting group description

Reporting group title

Cohort ( ≥ 7 to < 12 years of age) - For Core Study

Reporting group description

Subject analysis set title

Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase

Subject analysis set type

Safety analysis

Subject analysis set description

During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg perampanel. The maximum total daily dose a participant was allowed was 12 mg perampanel.

Subject analysis set title

Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase

Subject analysis set type

Safety analysis

Subject analysis set description

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

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End point title

Apparent Clearance (CL/F) of Perampanel [Core Study] ^[1]

End point description

CL/F was defined as the volume of plasma cleared of the drug per unit time. Blood samples were collected at Day 8, Day 36, Day 64 , and Day 78. The CL/F values were calculated for each visit and averaged to derive the total CL/F value per arm. Data was analyzed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/-standard deviation. The pharmacokinetic (PK) analysis set was used and was defined as participants with at least 1 PK assessment of perampanel with a documented dosing history.

End point type

Primary

End point timeframe

From Day 8 up to Day 78

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: No statistical analyses for this end point.

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	20	22
Units: Liters per hour
arithmetic mean (standard deviation)
Non-inducers (N = 14, 12)	0.732 ( 0.374 )	0.956 ( 0.4 )
Inducers (N = 6, 10)	1.73 ( 1.18 )	1.92 ( 0.517 )

No statistical analyses for this end point

Primary: Steady-state Average Concentration (Cav,ss) of Perampanel [Core Study]

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End point title

Steady-state Average Concentration (Cav,ss) of Perampanel [Core Study] ^[2]

End point description

C av,ss was calculated as 'Dose (mg)/Dosing Interval (24 h)/(CL/F [L/h]) x 1000'. C av,ss during a dosing interval was dose-normalized to 0.12 mg/kg in participants aged ≥ 2 to less than 12 years (intended to correspond to 8 mg/70 kg in adults/adolescents). Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. C av,ss values were calculated for each visit and averaged to derive the total C av,ss value per arm. Data was analysed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/- standard deviation. The PK analysis set was used and was defined as participants with at least 1 pharmacokinetic assessment of perampanel with a documented dosing history.

End point type

Primary

End point timeframe

From Day 8 up to Day 78

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: No statistical analyses for this end point.

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	20	22
Units: ng/mL
arithmetic mean (standard deviation)
Non-inducers (N = 14, 12)	179 ( 110 )	266 ( 220 )
Inducers (N = 6, 10)	96.8 ( 90.4 )	105 ( 38.9 )

No statistical analyses for this end point

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

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End point title

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

End point description

Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The seizure frequency per 28 days was calculated the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. The data is presented as median percent change +/- standard deviation. The full analysis set (FAS) was used and was defined as participants who received study drug, had any seizure frequency data during the 2-week Pretreatment Phase plus the 4 weeks prior to the Pretreatment Phase (Visit 1), and during the Treatment Phase of the Core Study.

End point type

Secondary

End point timeframe

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

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	22	28
Units: Percent change
median (full range (min-max))
Overall seizures	-43.6 (-100 to 95.4)	-33.9 (-100 to 1038.9)
Overall partial seizures	-82.5 (-100 to 95.4)	-46.8 (-100 to 1722.2)
Overall generalized seizures	-53.1 (-100 to 188.7)	305.4 (-62.9 to 1277.3)
Unclassified seizures	-73.7 (-100 to 217.3)	-67.3 (-100 to -34.6)

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	22	28
Units: Percent responders
number (not applicable)
Overall seizures	72.7	53.8
Overall partial seizures	82.4	60.9
Overall generalized seizures	76.9	33.3
Unclassified seizures	66.7	100

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Week 9 to Week 11

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	22	28
Units: Percentage of participants
number (not applicable)
Overall seizures	15	27.3
Simple Partial without Motor Signs	100	100
Simple Partial with Motor Signs	80	95.5
Complex Partial	80	50
Partial Seizures with SG	75	90.9
Overall Partial Seizures	50	45.5
Absence Generalized	95	90.9
Myoclonic Generalized	80	86.4
Clonic Generalized	100	100
Tonic Generalized	85	90.9
Tonic Clonic Generalized	80	90.9
Atonic Generalized	95	95.5
Overall Generalized Seizures	55	77.3
Unclassified Seizures	100	95.5

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Week 0 (Baseline), Week 11 or EOT

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	22	28
Units: Participants
number (not applicable)
Baseline - Normal, not at all ill (N=22, 27)	6	5
Baseline - Borderline mentally ill (N=22, 27)	0	0
Baseline - Mildly ill (N=22, 27)	3	4
Baseline - Moderately ill (N=22,27)	10	11
Baseline - Markedly ill (N=22, 27)	3	4
Baseline - Severely ill (N=22, 27)	0	3
Baseline - Extremely ill (N=22, 27)	0	0
EOT - Very much improved (N=22, 25)	6	7
EOT - Much improved (N=22, 25)	8	8
EOT - Minimally improved (N=22, 25)	5	5
EOT - No Change (N=22, 25)	2	3
EOT - Minimally worse (N=22, 25)	0	1
EOT - Much worse (N=22, 25)	0	1
EOT - Very much worse (N=22, 25)	1	0

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-Emergent Non-Serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel

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End point title

Number of Participants With Treatment-Emergent Non-Serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel

End point description

An AE was defined as any untoward medical occurrence in a participant administered with the study drug. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening (ie, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was as a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). In this study, treatment-emergent AEs (defined as an AE (serious/non-serious) that started/increased in severity on/after the first dose of study drug up to 30 days after the final dose of study drug) were assessed. The details of the adverse events are presented in the safety section of the results.

End point type

Secondary

End point timeframe

For each participant, from the first treatment dose till 30 days after the last dose or up to Week 15 for Core Study and Week 56 for the Extension Phase

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Number of subjects analysed	22	28	19	22
Units: Participants
number (not applicable)
Treatment-emergent non-serious AEs	22	25	19	22
Treatment-emergent SAEs	3	5	6	7

No statistical analyses for this end point

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

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End point title

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

End point description

The Palatability Questionnaire was answered directly by participants in Cohort ( ≥ 7 to < 12 years) and indirectly by participants in Cohort ( ≥ 2 to < 7 years) via their parents/caregivers. Participants selected their response from one of the five options (very good, good, not good-not bad, bad, very bad). The Safety Analysis Set was used and was defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Week 5 or at the time of early discontinuation

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	13	19
Units: Participants
number (not applicable)
Very good	3	3
Good	6	7
Not good, not bad	2	3
Bad	2	3
Very bad	0	3

No statistical analyses for this end point

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

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End point title

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

End point description

The Palatability Questionnaire was answered directly by participants in Cohort ( ≥ 7 to ≤ 12 years) and indirectly by participants in Cohort ( ≥ 2 to ≤ 7 years) via their parents/caregivers. Participants selected their response from one of the five options (very good, good, not good-not bad, bad, very bad). The Safety Analysis Set was used and was defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Week 5 or at the time of early discontinuation

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	13	19
Units: Participants
number (not applicable)
Very good	0	2
Good	5	3
Not good, not bad	7	13
Bad	1	0
Very bad	0	1

No statistical analyses for this end point

Secondary: Palatability Questionnaire Assessment - Based on Its Taste, Smell, and How it Felt in the Mouth, How Easy or Difficult Was it for You / Your Child to Take This Medicine Every Day [Core Study]

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End point title

Palatability Questionnaire Assessment - Based on Its Taste, Smell, and How it Felt in the Mouth, How Easy or Difficult Was it for You / Your Child to Take This Medicine Every Day [Core Study]

End point description

The Palatability Questionnaire was answered directly by participants in Cohort ( ≥ 7 to ≤ 12 years) and indirectly by participants in Cohort ( ≥ 2 to ≤ 7 years) via their parents/caregivers. Participants selected their response from one of the five options (very easy, easy, neither easy or difficult, difficult and very difficult). The Safety Analysis Set was used and was defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Week 5 or at the time of early discontinuation

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	14	19
Units: Participants
number (not applicable)
Very easy	6	7
Easy	5	7
Neither easy or difficult	3	3
Difficult	0	1
Very Difficult	0	1

No statistical analyses for this end point

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

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End point title

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

End point description

The Palatability Questionnaire was answered directly by participants in Cohort ( ≥ 7 to ≤ 12 years) and indirectly by participants in Cohort ( ≥ 2 to ≤ 7 years) via their parents/caregivers. Participants selected their response from one of the three options (yes, no and don't mind). The Safety Analysis Set was used and was defined as participants who received study drug treatment and had at least 1 postdose safety assessment.

End point type

Secondary

End point timeframe

Week 5 or at the time of early discontinuation

End point values	Cohort ( ≥ 2 to < 7 years of age) - For Core Study	Cohort ( ≥ 7 to < 12 years of age) - For Core Study
Number of subjects analysed	15	19
Units: Participants
number (not applicable)
Yes	4	9
No	2	5
Don't mind	9	5

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Baseline [Pretreatment Phase plus 4 weeks Prior to Visit 1], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Number of subjects analysed	19	22
Units: Percent change
median (full range (min-max))
Overall Seizures- Weeks 1-13	-58.74 (-100 to 75.8)	-39.59 (-100 to 759.3)
Overall Seizures- Weeks 14-26	-76.89 (-100 to 134.4)	-39.19 (-100 to 389.8)
Overall Seizures- Weeks 27-39; N=18, 20	-80.93 (-100 to 129.9)	-45.6 (-100 to 474.6)
Overall Seizures- Weeks 40-52; N=15, 15	-77.58 (-100 to -1.2)	-47.25 (-100 to 200)
Overall Partial Seizures- Weeks 1-13; N=14,19	-79.62 (-100 to 75.8)	-56.04 (-100 to 290.5)
Overall Partial Seizures- Weeks 14-26; N=14, 19	-78.69 (-100 to 134.4)	-67.3 (-100 to 87.9)
Overall Partial Seizures- Weeks 27-39; N=14, 17	-89.49 (-100 to 129.9)	-53.57 (-100 to 165.2)
Overall Partial Seizures- Weeks 40-52; N=14, 14	-89.89 (-100 to -1.2)	-39.46 (-100 to 100)
Overall Generalized Seizures- Weeks 1-13; N=11, 6	-63.96 (-100 to 465.5)	177.58 (-65 to 1065.4)
Overall Generalized Seizures- Weeks 14-26; N=11, 6	-79.08 (-100 to 440.7)	-14.13 (-87.3 to 389.8)
Overall Generalized Seizures- Weeks 27-39; N=10, 6	-73.93 (-100 to -8.9)	-4.77 (-83.6 to 474.6)
Overall Generalized Seizures- Weeks 40-52; N=7, 3	-76.91 (-100 to 182.8)	-5.86 (-61.5 to 700)
Unclassified Epileptic Seizure- Weeks 1-13; N=2, 1	-88.74 (-100 to -77.5)	-41.61 (-41.61 to -41.61)
Unclassified Epileptic Seizure- Weeks 14-26; N=2,1	-100 (-100 to -100)	-21.07 (-21.07 to -21.07)
Unclassified Epileptic Seizure- Weeks 27-39; N=2,1	-58.24 (-100 to -16.5)	6.81 (6.81 to 6.81)
Unclassified Epileptic Seizure- Weeks 40-52; N=2,1	-100 (-100 to -100)	-73.21 (-73.21 to -73.21)

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Baseline [Pretreatment Phase plus 4 weeks Prior to Visit 1], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Number of subjects analysed	19	22
Units: Percentage of responders
number (not applicable)
Overall Seizures- Weeks 1-13	57.9	45.5
Overall Seizures- Weeks 14-26	84.2	45.5
Overall Seizures- Weeks 27-39; N=18, 20	77.8	45
Overall Seizures- Weeks 40-52; N=15, 15	80	46.7
Overall Partial Seizures- Weeks 1-13; N=14,19	64.3	57.9
Overall Partial Seizures- Weeks 14-26; N=14, 19	85.7	57.9
Overall Partial Seizures- Weeks 27-39; N=14, 17	92.9	52.9
Overall Partial Seizures- Weeks 40-52; N=14, 14	71.4	42.9
Overall Generalized Seizures- Weeks 1-13; N=11, 6	72.7	16.7
Overall Generalized Seizures- Weeks 14-26; N=11, 6	81.8	33.3
Overall Generalized Seizures- Weeks 27-39; N=10, 6	70	16.7
Overall Generalized Seizures- Weeks 40-52; N=7, 3	71.4	33.3
Unclassified Epileptic Seizure- Weeks 1-13; N=2, 1	100	0
Unclassified Epileptic Seizure- Weeks 14-26; N=2,1	100	0
Unclassified Epileptic Seizure- Weeks 27-39; N=2,1	50	0
Unclassified Epileptic Seizure- Weeks 40-52; N=2,1	100	100

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Number of subjects analysed	19	22
Units: Percentage of participants
number (not applicable)
Overall Seizures- Weeks 1-13	21.1	22.7
Overall Seizures- Weeks 14-26;N=18, 20	22.2	30
Overall Seizures- Weeks 27-39; N=15, 15	13.3	33.3
Overall Seizures- Weeks 40-52; N=11, 11	27.3	36.4
Overall Partial Seizures- Weeks 1-13	52.6	40.9
Overall Partial Seizures- Weeks 14-26; N=18, 20	55.6	45
Overall Partial Seizures- Weeks 27-39; N=15, 15	33.3	40
Overall Partial Seizures- Weeks 40-52; N=11, 11	36.4	45.5
Overall Generalized Seizures- Weeks 1-13	57.9	72.7
Overall Generalized Seizures- Weeks 14-26; N=18,20	55.6	75
Overall Generalized Seizures- Weeks 27-39; N=15,15	66.7	80
Overall Generalized Seizures- Weeks 40-52; N=11,11	63.6	90.9
Unclassified Epileptic Seizure- Weeks 1-13	100	90.9
Unclassified Epileptic Seizure-Weeks 14-26;N=18,20	100	95
Unclassified Epileptic Seizure-Weeks 27-39;N=15,15	93.3	93.3
Unclassified Epileptic Seizure-Weeks 40-52;N=11,11	100	90.9

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Number of subjects analysed	19	22
Units: Participants
number (not applicable)
Baseline- Normal, not at all ill	5	3
Baseline- Borderline mentally ill	0	0
Baseline- Mildly ill	3	4
Baseline- Moderately ill	10	10
Baseline- Markedly ill	1	4
Baseline- Severely ill	0	1
Baseline- Extremely ill	0	0
Week 11- Very much improved; N=19, 21	6	7
Week 11- Much improved; N=19, 21	8	7
Week 11- Minimally improved; N=19, 21	3	5
Week 11- No change; N= 19, 21	2	2
Week 11- Minimally worse; N=19, 21	0	0
Week 11- Much worse; N=19, 21	0	0
Week 11- Very much worse; N=19, 21	0	0
Week 28- Very much improved; N=18, 19	5	4
Week 28- Much improved; N=18, 19	7	8
Week 28- Minimally improved; N=18, 19	2	3
Week 28- No change; N=18, 19	4	3
Week 28- Minimally worse; N=18, 19	0	1
Week 28- Much worse; N=18, 19	0	0
Week 28- Very much worse; N=18, 19	0	0
Week 52- Very much improved; N=14, 12	1	3
Week 52- Much improved; N=14, 12	7	5
Week 52- Minimally improved; N=14, 12	4	4
Week 52- No change; N=14, 12	1	0
Week 52- Minimally worse; N=14, 12	0	0
Week 52- Much worse; N=14, 12	1	0
Week 52- Very much worse; N=14, 12	0	0
EOT- Very much improved	1	4
EOT- Much improved	8	9
EOT- Minimally improved	5	6
EOT- No change	4	2
EOT- Minimally worse	0	1
EOT- Much worse	1	0
EOT- Very much worse	0	0

No statistical analyses for this end point

Other pre-specified: The Effect of Demographics on Population PK Parameters: Area Under the Concentration-Time Curve (AUC)

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End point title

The Effect of Demographics on Population PK Parameters: Area Under the Concentration-Time Curve (AUC)

End point description

This outcome was not assessed for this study.

End point type

Other pre-specified

End point timeframe

11 weeks

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study
Number of subjects analysed	0 ^[3]	0 ^[4]
Units: ng*hr/mL
geometric mean (standard deviation)	( )	( )

Notes
[3] - This outcome was not assessed for this study.
[4] - This outcome was not assessed for this study.

No statistical analyses for this end point

Other pre-specified: The Effect of Demographics on Population PK Parameters: Cmax

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End point title

The Effect of Demographics on Population PK Parameters: Cmax

End point description

This outcome was not assessed in the study.

End point type

Other pre-specified

End point timeframe

11 weeks

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study
Number of subjects analysed	0 ^[5]	0 ^[6]
Units: ng/mL
geometric mean (standard deviation)	( )	( )

Notes
[5] - This outcome was not assessed for this study.
[6] - This outcome was not assessed for this study.

No statistical analyses for this end point

Other pre-specified: The Effect of Demographics on Population PK Parameters: Time to Reach Cmax (Tmax)

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End point title

The Effect of Demographics on Population PK Parameters: Time to Reach Cmax (Tmax)

End point description

This outcome was not assessed for this study.

End point type

Other pre-specified

End point timeframe

11 weeks

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study
Number of subjects analysed	0 ^[7]	0 ^[8]
Units: Hours
geometric mean (standard deviation)	( )	( )

Notes
[7] - This outcome was not assessed for this study.
[8] - This outcome was not assessed for this study.

No statistical analyses for this end point

Other pre-specified: The Effect of the Most Common Concomitant Antiepileptic Drugs (AEDs) on Population PK Parameters: AUC

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End point title

The Effect of the Most Common Concomitant Antiepileptic Drugs (AEDs) on Population PK Parameters: AUC

End point description

This outcome was not assessed for this study.

End point type

Other pre-specified

End point timeframe

11 weeks

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study
Number of subjects analysed	0 ^[9]	0 ^[10]
Units: ng*hr/mL
geometric mean (standard deviation)	( )	( )

Notes
[9] - This outcome was not assessed for this study.
[10] - This outcome was not assessed for this study.

No statistical analyses for this end point

Other pre-specified: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Maximum Drug Concentration (Cmax)

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End point title

The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Maximum Drug Concentration (Cmax)

End point description

This outcome was not assessed for this study.

End point type

Other pre-specified

End point timeframe

11 weeks

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study
Number of subjects analysed	0 ^[11]	0 ^[12]
Units: ng/mL
geometric mean (standard deviation)	( )	( )

Notes
[11] - This outcome was not assessed for this study.
[12] - This outcome was not assessed for this study.

No statistical analyses for this end point

Other pre-specified: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Tmax

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End point title

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

End point description

This outcome was not assessed for this study.

End point type

Other pre-specified

End point timeframe

11 weeks

End point values	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study
Number of subjects analysed	0 ^[13]	0 ^[14]
Units: Hours
geometric mean (standard deviation)	( )	( )

Notes
[13] - This outcome was not assessed for this study.
[14] - This outcome was not assessed for this study.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

For each participant, from the first treatment dose till 30 days after the last dose or up to Week 15 for Core Study and Week 56 for the Extension Phase

Adverse event reporting additional description

Treatment-emergent adverse events (TEAEs) are presented in this section. The Safety Analysis Set included all subjects who took at least 1 dose of perampanel and had at least 1 postdose safety assessment during the Core Study and the Extension Phase.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study

Reporting group description

During the titration period, participants started at a set daily dose of 0.015 mg/kg perampanel oral suspension, once daily, and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period.

Reporting group title

Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study

Reporting group description

Reporting group title

Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase

Reporting group description

During the extension phase, participants continued taking perampanel oral suspension, once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg perampanel.

Reporting group title

Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase

Reporting group description

Serious adverse events	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 22 (13.64%)	5 / 28 (17.86%)	6 / 19 (31.58%)	7 / 22 (31.82%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Investigations
Anticonvulsant Drug Level Increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)
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
Congenital, familial and genetic disorders
Developmental Hip Dysplasia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (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
Vascular disorders
Hypotension
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cyanosis
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 2	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Status Epilepticus
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cyclic Vomiting Syndrome
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (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
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Failure
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Abnormal Behaviour
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mental Status Changes
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Foot Deformity
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)
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
Muscle Contracture
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)
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
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis Externa
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis Media Acute
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Syncytial Virus Bronchiolitis
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	0 / 19 (0.00%)	0 / 22 (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
Septic Shock
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis Media
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (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
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cohort ( ≥ 2 to < 7 Years of Age) - For Core Study	Cohort ( ≥ 7 to < 12 Years of Age) - For Core Study	Cohort ( ≥ 2 to < 7 Years of Age) - For Extension Phase	Cohort ( ≥ 7 to < 12 Years of Age) - For Extension Phase
Total subjects affected by non serious adverse events
subjects affected / exposed	22 / 22 (100.00%)	25 / 28 (89.29%)	19 / 19 (100.00%)	22 / 22 (100.00%)
Vascular disorders
Hypotension
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 22 (4.55%)	8 / 28 (28.57%)	1 / 19 (5.26%)	6 / 22 (27.27%)
occurrences all number	5	9	6	6
Gait Disturbance
subjects affected / exposed	2 / 22 (9.09%)	1 / 28 (3.57%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	2	1	2	0
Irritability
subjects affected / exposed	3 / 22 (13.64%)	5 / 28 (17.86%)	3 / 19 (15.79%)	5 / 22 (22.73%)
occurrences all number	3	5	3	5
Pyrexia
subjects affected / exposed	8 / 22 (36.36%)	4 / 28 (14.29%)	8 / 19 (42.11%)	7 / 22 (31.82%)
occurrences all number	10	4	10	6
Immune system disorders
Autoimmune Disorder
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Hypersensitivity
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Reproductive system and breast disorders
Vulval Disorder
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 22 (13.64%)	1 / 28 (3.57%)	4 / 19 (21.05%)	2 / 22 (9.09%)
occurrences all number	5	1	5	2
Nasal Congestion
subjects affected / exposed	2 / 22 (9.09%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	2	0	2	0
Rhinorrhoea
subjects affected / exposed	2 / 22 (9.09%)	0 / 28 (0.00%)	3 / 19 (15.79%)	1 / 22 (4.55%)
occurrences all number	2	0	3	2
Asthma
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	0	0	2	0
Oropharyngeal pain
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	0	0	4
Psychiatric disorders
Aggression
subjects affected / exposed	3 / 22 (13.64%)	1 / 28 (3.57%)	5 / 19 (26.32%)	2 / 22 (9.09%)
occurrences all number	3	1	5	3
Anxiety
subjects affected / exposed	2 / 22 (9.09%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	3	0	3	0
Insomnia
subjects affected / exposed	1 / 22 (4.55%)	2 / 28 (7.14%)	1 / 19 (5.26%)	2 / 22 (9.09%)
occurrences all number	1	3	2	6
Oppositional Defiant Disorder
subjects affected / exposed	2 / 22 (9.09%)	1 / 28 (3.57%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	2	1	2	1
Tearfulness
subjects affected / exposed	2 / 22 (9.09%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	2	0	2	0
Abnormal Behaviour
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	0	0	1	1
Investigations
Thyroxine Decreased
subjects affected / exposed	0 / 22 (0.00%)	2 / 28 (7.14%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	2	0	2
Weight Increased
subjects affected / exposed	1 / 22 (4.55%)	3 / 28 (10.71%)	1 / 19 (5.26%)	4 / 22 (18.18%)
occurrences all number	1	3	1	4
Blood Bicarbonate Decreased
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Blood Sodium Decreased
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Blood Triglycerides Increased
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Blood Uric Acid Decreased
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	2	0	2	1
Cardiac Murmur
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	2	0
Cardiac Murmur Functional
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Globulins Decreased
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Heart Rate Increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Tri-Iodothyronine Decreased
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Weight Decreased
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	1	0	2	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 22 (9.09%)	1 / 28 (3.57%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	2	1	3	2
Contusion
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Epiphyseal Fracture
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Head Injury
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Laceration
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Ligament Sprain
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	2	0	2
Congenital, familial and genetic disorders
Phimosis
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Ataxia
subjects affected / exposed	0 / 22 (0.00%)	2 / 28 (7.14%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	2	0	2
Balance Disorder
subjects affected / exposed	1 / 22 (4.55%)	2 / 28 (7.14%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	2	1	1
Dizziness
subjects affected / exposed	3 / 22 (13.64%)	2 / 28 (7.14%)	3 / 19 (15.79%)	2 / 22 (9.09%)
occurrences all number	3	2	6	4
Headache
subjects affected / exposed	1 / 22 (4.55%)	2 / 28 (7.14%)	2 / 19 (10.53%)	3 / 22 (13.64%)
occurrences all number	1	3	4	5
Lethargy
subjects affected / exposed	1 / 22 (4.55%)	2 / 28 (7.14%)	4 / 19 (21.05%)	3 / 22 (13.64%)
occurrences all number	1	2	4	3
Psychomotor Hyperactivity
subjects affected / exposed	0 / 22 (0.00%)	2 / 28 (7.14%)	0 / 19 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	4	0	0
Somnolence
subjects affected / exposed	4 / 22 (18.18%)	3 / 28 (10.71%)	3 / 19 (15.79%)	3 / 22 (13.64%)
occurrences all number	8	3	16	6
Tremor
subjects affected / exposed	0 / 22 (0.00%)	2 / 28 (7.14%)	0 / 19 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	2	0	0
Cognitive Disorder
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	1	0	2	0
Drooling
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Dyskinesia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Hypotonia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Intention Tremor
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Sedation
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Speech Disorder
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Agitation
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	1	1	0
Depressed Mood
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	0	1	1	1
Disorientation
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Echolalia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Emotional Disorder
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	0	0	3	0
Hallucination
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Mood Altered
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	1	1	0
Mood Swings
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	1	0	2
Sleep Disorder
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	1	0	3	1
Suicidal Ideation
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	1 / 19 (5.26%)	2 / 22 (9.09%)
occurrences all number	0	1	1	2
Epistaxis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	0	1	2	1
Grunting
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	2	0	1	0
Rhinitis Allergic
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	0	1	1	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Neutropenia
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	0	0	2
Thrombocytopenia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	1	0	2	1
Ear and labyrinth disorders
Ear Pain
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Eye disorders
Conjunctivitis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	0	1	1	1
Eye Irritation
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Ocular Hyperaemia
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	1	1	1
Photophobia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Gastrointestinal disorders
Abdominal Pain Upper
subjects affected / exposed	0 / 22 (0.00%)	4 / 28 (14.29%)	0 / 19 (0.00%)	5 / 22 (22.73%)
occurrences all number	0	7	0	10
Vomiting
subjects affected / exposed	3 / 22 (13.64%)	5 / 28 (17.86%)	4 / 19 (21.05%)	6 / 22 (27.27%)
occurrences all number	3	8	5	10
Abdominal Pain
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	0	0	2
Aphthous Stomatitis
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Constipation
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	1	2	1
Diarrhoea
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	3 / 19 (15.79%)	1 / 22 (4.55%)
occurrences all number	1	1	3	2
Flatulence
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Gingival Recession
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Nausea
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	2 / 19 (10.53%)	2 / 22 (9.09%)
occurrences all number	1	1	2	2
Oral Mucosal Discolouration
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Skin and subcutaneous tissue disorders
Dermatitis Contact
subjects affected / exposed	1 / 22 (4.55%)	2 / 28 (7.14%)	1 / 19 (5.26%)	2 / 22 (9.09%)
occurrences all number	1	2	1	2
Eczema
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	1	1	1
Rash
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	0	0	2	2
Skin Disorder
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Urticaria
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	0	0	3	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Enuresis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	1	0	2
Haematuria
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Proteinuria
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Pain In Extremity
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Posture Abnormal
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Infections and infestations
Ear Infection
subjects affected / exposed	0 / 22 (0.00%)	2 / 28 (7.14%)	3 / 19 (15.79%)	4 / 22 (18.18%)
occurrences all number	0	2	3	4
Otitis Media
subjects affected / exposed	2 / 22 (9.09%)	2 / 28 (7.14%)	2 / 19 (10.53%)	3 / 22 (13.64%)
occurrences all number	3	2	8	7
Upper Respiratory Tract Infection
subjects affected / exposed	3 / 22 (13.64%)	2 / 28 (7.14%)	5 / 19 (26.32%)	6 / 22 (27.27%)
occurrences all number	3	4	11	10
Atypical Pneumonia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Bronchitis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	0 / 19 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	1	0	2
Clostridium Difficile Infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Fungal Skin Infection
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Gastroenteritis Viral
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	0	0	1	1
Influenza
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	0	2	1
Lice Infestation
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	0	1	1
Nasopharyngitis
subjects affected / exposed	1 / 22 (4.55%)	1 / 28 (3.57%)	3 / 19 (15.79%)	3 / 22 (13.64%)
occurrences all number	1	2	4	5
Pharyngitis
subjects affected / exposed	0 / 22 (0.00%)	1 / 28 (3.57%)	1 / 19 (5.26%)	3 / 22 (13.64%)
occurrences all number	0	1	1	3
Sinusitis
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)
occurrences all number	1	0	2	2
Tinea Capitis
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Urinary Tract Infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	2	0
Viral Rash
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	1 / 22 (4.55%)	2 / 28 (7.14%)	2 / 19 (10.53%)	1 / 22 (4.55%)
occurrences all number	1	3	3	2
Increased Appetite
subjects affected / exposed	0 / 22 (0.00%)	3 / 28 (10.71%)	1 / 19 (5.26%)	4 / 22 (18.18%)
occurrences all number	0	3	1	4
Dehydration
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Hypernatraemia
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	1	0	1	0
Metabolic Acidosis
subjects affected / exposed	1 / 22 (4.55%)	0 / 28 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)
occurrences all number	2	0	2	0
Vitamin D Deficiency
subjects affected / exposed	0 / 22 (0.00%)	0 / 28 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0

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Were there any global substantial amendments to the protocol? Yes

03 Apr 2012

In addition to minor administrative changes, Amendment 01 dated 03 Apr 2012 made the following changes to the protocol: • Addition of the Palatability Questionnaire • Revised the corrected QT interval to QTcF • Addition of the Clinical Global Impression (CGI) referencing • Deletion of the CGI appendix • Added text regarding the telephone interview At the time of Amendment 01, 9 subjects had been enrolled in the study.

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

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

Primary: Steady-state Average Concentration (Cav,ss) of Perampanel [Core Study]

Primary: Steady-state Average Concentration (Cav,ss) of Perampanel [Core Study]

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

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

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

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

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

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

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

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

Secondary: Number of Participants With Treatment-Emergent Non-Serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel

Secondary: Number of Participants With Treatment-Emergent Non-Serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel

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

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

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

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

Secondary: Palatability Questionnaire Assessment - Based on Its Taste, Smell, and How it Felt in the Mouth, How Easy or Difficult Was it for You / Your Child to Take This Medicine Every Day [Core Study]

Secondary: Palatability Questionnaire Assessment - Based on Its Taste, Smell, and How it Felt in the Mouth, How Easy or Difficult Was it for You / Your Child to Take This Medicine Every Day [Core Study]

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

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

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

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

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

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

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

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

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

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

Other pre-specified: The Effect of Demographics on Population PK Parameters: Area Under the Concentration-Time Curve (AUC)

Other pre-specified: The Effect of Demographics on Population PK Parameters: Area Under the Concentration-Time Curve (AUC)

Other pre-specified: The Effect of Demographics on Population PK Parameters: Cmax

Other pre-specified: The Effect of Demographics on Population PK Parameters: Cmax

Other pre-specified: The Effect of Demographics on Population PK Parameters: Time to Reach Cmax (Tmax)

Other pre-specified: The Effect of Demographics on Population PK Parameters: Time to Reach Cmax (Tmax)

Other pre-specified: The Effect of the Most Common Concomitant Antiepileptic Drugs (AEDs) on Population PK Parameters: AUC

Other pre-specified: The Effect of the Most Common Concomitant Antiepileptic Drugs (AEDs) on Population PK Parameters: AUC

Other pre-specified: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Maximum Drug Concentration (Cmax)

Other pre-specified: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Maximum Drug Concentration (Cmax)

Other pre-specified: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Tmax

Other pre-specified: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Tmax

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information