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Clinical Trial Results:
Open-Label, Single-Arm, Multicenter, Long-Term Study to Evaluate Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Pediatric Subjects with Epilepsy

Summary
EudraCT number	2011-000374-60
Trial protocol	BE CZ ES PL Outside EU/EEA IE GB DE HU NL FR IT
Global end of trial date	03 Feb 2022

Results information
Results version number	v1
This version publication date	13 Aug 2022
First version publication date	13 Aug 2022
Other versions	v2

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

N01266

ISRCTN number

US NCT number

NCT01364597

WHO universal trial number (UTN)

Sponsor organisation name

UCB Pharma SA

Sponsor organisation address

Allée de la Recherche 60, Brussels, Belgium, 1070

Public contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Scientific contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000332-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

09 Mar 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

Document the long-term safety and tolerability of BRV

Protection of trial subjects

During the conduct of the study all participants were closely monitored

Background therapy

Background therapy as permitted in the protocol

Evidence for comparator

N/A

Actual start date of recruitment

01 Aug 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 12

Country: Number of subjects enrolled

Czechia: 12

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Hungary: 30

Country: Number of subjects enrolled

Italy: 4

Country: Number of subjects enrolled

Mexico: 61

Country: Number of subjects enrolled

Poland: 56

Country: Number of subjects enrolled

Spain: 25

Country: Number of subjects enrolled

United States: 55

Worldwide total number of subjects

257

EEA total number of subjects

141

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)

156

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

The study started to enroll participants in August 2011 and concluded in February 2022.

Screening details

The Participant Flow refers to the enrolled set.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Age Cohort: ≥1 month to <2 years

Arm description

Participants from core study (LTFU [Long term follow-up] participants from N01263 [NCT00422422], EP0065 [NCT03405714] or N01349 [NCT03325439]) aged greater than or equal to (≥) 1 month to less than (<) 2 years entered evaluation period (EP) and received individualized Brivaracetam (BRV) dose as they were receiving at completion of core study. For all participants, the approximate BRV doses to be administered are 1 to 5 milligrams per kilogram per day (mg/kg/day) (0.5, 1, 2, and 2.5 mg/kg twice daily[bid]), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5 mg/kg bid), not to exceed a dose of 200 mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the investigational medicinal product (IMP) development was stopped by the Sponsor.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

UCB 34714

Other name

Pharmaceutical forms

Oral solution, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received BRV at pre-specified dose and time points.

Age Cohort: ≥2 to <4 years

Arm description

Participants from core study (LTFU participants from N01263 [NCT00422422] and EP0065 [NCT03405714]) aged ≥2 Years to <4 years entered EP and received individualized BRV dose as they were receiving at completion of core study. For all participants, the approximate BRV doses to be administered are 1 to 5 mg/kg/day (0.5, 1, 2, and 2.5mg/kg bid), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5mg/kg bid), not to exceed a dose of 200mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the IMP development was stopped by the Sponsor.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

UCB 34714

Other name

Pharmaceutical forms

Oral solution, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received BRV at pre-specified dose and time points..

Age Cohort: ≥4 to <12 years

Arm description

Participants from core study (LTFU participants from N01263 [NCT00422422] and EP0065 [NCT03405714]) aged ≥4 Years to <12 years entered EP and received individualized BRV dose as they were receiving at completion of core study and Directly Enrolled (DE) participants in this study aged ≥4 years to <12 years of age received BRV dose based on tolerability confirmed during screening period. For all participants, the approximate BRV doses to be administered are 1 to 5 mg/kg/day (0.5, 1, 2, and 2.5mg/kg bid), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5 mg/kg bid), not to exceed a dose of 200 mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the IMP development was stopped by the Sponsor.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

UCB 34714

Other name

Pharmaceutical forms

Oral solution, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received BRV at pre-specified dose and time points.

Age Cohort: ≥12 to <17 years

Arm description

Participants from core study (LTFU participants from N01263 [NCT00422422] and EP0065 [NCT03405714]) aged ≥12 Years to <17 years entered EP and received individualized BRV dose as they were receiving at completion of core study and DE participants in this study aged ≥12 years to <17 years of age received BRV dose based on tolerability confirmed during screening period. For all participants, the approximate BRV doses to be administered are 1 to 5 mg/kg/day (0.5, 1, 2, and 2.5 mg/kg bid), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5 mg/kg bid), not to exceed a dose of 200 mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the IMP development was stopped by the Sponsor.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

UCB 34714

Other name

Pharmaceutical forms

Oral solution, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received BRV at pre-specified dose and time points.

Number of subjects in period 1	Age Cohort: ≥1 month to <2 years	Age Cohort: ≥2 to <4 years	Age Cohort: ≥4 to <12 years	Age Cohort: ≥12 to <17 years
Started	36	15	141	65
Directly Enrolled (DE) Participants	0 ^[1]	0 ^[2]	85	35 ^[3]
Long-term Follow-up (LTFU) Participants	36	15	56 ^[4]	30 ^[5]
Completed	18	4	65	37
Not completed	18	11	76	28
Patient became seizure-free after surgery	-	-	1	-
Patient cured from Epilepsy	-	-	1	-
Seizures resolved	-	-	1	-
Cure	1	-	-	-
Lack of compliance	1	-	-	-
Lack of reliability from the subject's caregiver	1	-	-	-
Sponsor recommended discontinuation	-	-	-	1
Patient was moving	-	1	-	-
End of treatment epilepsy	1	-	-	-
5 year without seizures. Treatment is finish	-	-	1	-
Consent withdrawn by subject	4	1	18	6
Adverse event, non-fatal	4	5	16	7
Dropout	-	-	3	1
Non compliance	1	-	1	-
Unknown	-	-	-	1
No Seizures	1	-	-	-
Investigator decision	-	-	1	-
Parents went abroad with the patient	-	-	1	-
Lost to follow-up	-	-	5	3
Unreliable subject	-	-	-	1
Lack of efficacy	4	4	23	8
Protocol deviation	-	-	2	-
BRV discontinued as no seizures during 2 years	-	-	1	-
BRV administration dropout	-	-	1	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at this arm is the sum of both the milestones ‘Directly Enrolled (DE) Participants and Long-term Follow-up (LTFU) Participants’ and equals to the started participants only. Hence the number of participants at each of intermediate milestones were lesser.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at this arm is the sum of both the milestones ‘Directly Enrolled (DE) Participants and Long-term Follow-up (LTFU) Participants’ and equals to the started participants only. Hence the number of participants at each of intermediate milestones were lesser.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at this arm is the sum of both the milestones ‘Directly Enrolled (DE) Participants and Long-term Follow-up (LTFU) Participants’ and equals to the started participants only. Hence the number of participants at each of intermediate milestones were lesser.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at this arm is the sum of both the milestones ‘Directly Enrolled (DE) Participants and Long-term Follow-up (LTFU) Participants’ and equals to the started participants only. Hence the number of participants at each of intermediate milestones were lesser.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of participants at this arm is the sum of both the milestones ‘Directly Enrolled (DE) Participants and Long-term Follow-up (LTFU) Participants’ and equals to the started participants only. Hence the number of participants at each of intermediate milestones were lesser.

Baseline characteristics

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Reporting group title

Age Cohort: ≥1 month to <2 years

Reporting group description

Reporting group title

Age Cohort: ≥2 to <4 years

Reporting group description

Reporting group title

Age Cohort: ≥4 to <12 years

Reporting group description

Reporting group title

Age Cohort: ≥12 to <17 years

Reporting group description

Reporting group values	Age Cohort: ≥1 month to <2 years	Age Cohort: ≥2 to <4 years	Age Cohort: ≥4 to <12 years	Age Cohort: ≥12 to <17 years	Total
Number of subjects	36	15	141	65	257
Age Categorical
Units: Participants
Infants and toddlers (28 days-23 months)	36	0	0	0	36
Children (2-11 years)	0	15	141	0	156
Adolescents (12-17 years)	0	0	0	65	65
Age Continuous
Units: years
arithmetic mean (standard deviation)	1.122 ( 0.504 )	2.761 ( 0.582 )	7.699 ( 2.394 )	13.824 ( 1.274 )	-
Gender Categorical
Units: Subjects
Female	19	5	62	30	116
Male	17	10	79	35	141

End points

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Reporting group title

Age Cohort: ≥1 month to <2 years

Reporting group description

Reporting group title

Age Cohort: ≥2 to <4 years

Reporting group description

Reporting group title

Age Cohort: ≥4 to <12 years

Reporting group description

Reporting group title

Age Cohort: ≥12 to <17 years

Reporting group description

Subject analysis set title

Brivaracetam (BRV): Participants ≥ 2 years to <17 years

Subject analysis set type

Full analysis

Subject analysis set description

Participants from core study (LTFU participants from N01263 [NCT00422422]) aged ≥2 Years to <17 years entered EP and received individualized BRV dose as they were receiving at completion of core study and DE participants in this study aged ≥4 years to <17 years of age received BRV dose based on tolerability confirmed during screening period. For all participants, the approximate BRV doses to be administered are 1 to 5 mg/kg/day (0.5, 1, 2, and 2.5 mg/kg bid), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5 mg/kg bid), not to exceed a dose of 200 mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the IMP development was stopped by the Sponsor.

Subject analysis set title

Brivaracetam (BRV): Participants ≥1 month to <2 years

Subject analysis set type

Full analysis

Subject analysis set description

Participants from core study (LTFU [Long term follow-up] participants from N01263 [NCT00422422] or N01349 [NCT03325439]) aged ≥1 month to <2 years entered EP and received individualized BRV dose as they were receiving at completion of core study. For all participants, the approximate BRV doses to be administered are 1 to 5 mg/kg/day (0.5, 1, 2, and 2.5 mg/kg bid), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5 mg/kg bid), not to exceed a dose of 200 mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the IMP development was stopped by the Sponsor.

Primary: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study

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End point title

Percentage of participants with treatment-emergent adverse events (TEAEs) during the study ^[1]

End point description

TEAEs are defined as AEs that had onset on or after the day of first BRV dose. The Safety Set (SS) consisted of all enrolled participants who took at least 1 dose of study medication.

End point type

Primary

End point timeframe

From Baseline to end of study (up to 10 years)

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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.

End point values	Age Cohort: ≥1 month to <2 years	Age Cohort: ≥2 to <4 years	Age Cohort: ≥4 to <12 years	Age Cohort: ≥12 to <17 years
Number of subjects analysed	36	15	141	65
Units: percentage of participants
number (not applicable)	94.4	93.3	93.6	92.3

No statistical analyses for this end point

Primary: Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study

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End point title

Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study ^[2]

End point description

TEAEs: AEs that had onset on or after day of first BRV dose. SAE: an event that met 1 or more of below criteria: a) Death, b) Life-threatening, (excluding reaction that might caused death had it occurred in more severe form.) c) Significant or persistent disability/incapacity, d) Congenital anomaly/birth defect (including that occurring in fetus), e) Important medical event that, based upon appropriate medical judgment, may have jeopardized participant and required medical or surgical intervention to prevent 1 of other outcomes listed in definition of serious, (Important medical events may have included allergic bronchospasm requiring intensive treatment in an emergency room [ER] or at home) f) Initial inpatient hospitalization or prolongation of hospitalization. (Participant admitted to hospital, even if released on same day, met criteria for initial inpatient hospitalization). Safety Set (SS) consisted of all enrolled participants who took at least 1 dose of study medication.

End point type

Primary

End point timeframe

From Baseline to end of study (up to 10 years)

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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.

End point values	Age Cohort: ≥1 month to <2 years	Age Cohort: ≥2 to <4 years	Age Cohort: ≥4 to <12 years	Age Cohort: ≥12 to <17 years
Number of subjects analysed	36	15	141	65
Units: percentage of participants
number (not applicable)	38.9	53.3	29.8	29.2

No statistical analyses for this end point

Secondary: Absolute change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on daily record card [DRC])

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End point title

Absolute change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on daily record card [DRC])

End point description

Absolute change in seizure frequency per 28 days based on DRC data, is calculated as baseline seizure frequency per 28 days minus post-Baseline seizure frequency per 28 days. The 28-day adjusted seizure frequency was calculated by dividing number of POS by number of days for which the diary was completed and multiplying resulting value by 28. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM and it differs in both absolute and percent change because the percent change cannot be calculated for participants with 0 baseline ADF. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded. This OM was analyzed in participants ≥2 years (per DRC data) only.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous study N01263 [NCT00422422]; and DE participants: Baseline of current study) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥ 2 years to <17 years
Number of subjects analysed	134
Units: seizure frequency per 28-days
arithmetic mean (standard deviation)	-37.48 ( 628.34 )

No statistical analyses for this end point

Secondary: Percent change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on DRC data)

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End point title

Percent change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on DRC data)

End point description

Percent change is calculated as absolute change in seizure frequency per 28 days divided by baseline seizure frequency per 28 days multiplied to 100. The 28 day adjusted seizure frequency was calculated by dividing the number of partial seizures by the number of days for which the diary was completed, and multiplying the resulting value by 28. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM and it differs in both absolute and percent change because the percent change cannot be calculated for participants with 0 baseline ADF. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded. This OM was analyzed in participants ≥2 years (per DRC data) only.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous study N01263 [NCT00422422]; and DE participants: Baseline of current study) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥ 2 years to <17 years
Number of subjects analysed	105
Units: percent change
arithmetic mean (standard deviation)	26.57 ( 123.06 )

No statistical analyses for this end point

Secondary: 50% responder rate for participants ≥2 years of age for total seizures (all types) (based on DRC data)

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End point title

50% responder rate for participants ≥2 years of age for total seizures (all types) (based on DRC data)

End point description

A responder is defined as a participant with a ≥ 50% reduction in seizure frequency from the baseline period of the previous study for LTFU participants or during this study for DE participants. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded. This OM was analyzed in participants ≥2 years (per DRC data) only.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous study N01263 [NCT00422422]; and DE participants: Baseline of current study) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥ 2 years to <17 years
Number of subjects analysed	167
Units: percentage of participants
number (not applicable)	50.9

No statistical analyses for this end point

Secondary: Absolute change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

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End point title

Absolute change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

End point description

Absolute change in ADF is calculated as the baseline ADF minus post-baseline ADF. ADF is calculated as (number of seizures from central reader divided by stop date and time of EEG minus start date and time of EEG) multiplied to 60, multiplied to 24. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM and it differs in both absolute and percent change because the percent change cannot be calculated for participants with 0 baseline ADF. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded. This OM was analyzed in participants <2 years (per EEG data) only.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422], or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥1 month to <2 years
Number of subjects analysed	8
Units: seizures per day
arithmetic mean (standard deviation)	2.56 ( 4.44 )

No statistical analyses for this end point

Secondary: Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

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End point title

Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

End point description

Percent change in average daily frequency (ADF) is calculated as absolute change in ADF divided by baseline ADF multiplied to 100. ADF is calculated as (number of seizures from central reader divided by stop date and time of EEG minus start date and time of EEG) multiplied to 60, multiplied to 24. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM and it differs in both absolute and percent change because the percent change cannot be calculated for participants with 0 baseline ADF. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded. This OM was analyzed in participants <2 years (per EEG data) only.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422], or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥1 month to <2 years
Number of subjects analysed	3
Units: Percent change
arithmetic mean (standard deviation)	98.72 ( 2.22 )

No statistical analyses for this end point

Secondary: 50% responder rate for participants <2 years of age for total seizures (all types) (based on EEG data)

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End point title

50% responder rate for participants <2 years of age for total seizures (all types) (based on EEG data)

End point description

A responder is defined as a participant with a ≥ 50% reduction in seizure frequency from the baseline period of the previous study for LTFU participants. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded. This OM was analyzed in participants <2 years (per EEG data) only.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422], or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥1 month to <2 years
Number of subjects analysed	8
Units: percentage of participants
number (not applicable)	75.0

No statistical analyses for this end point

Secondary: Percent change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

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End point title

Percent change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

End point description

Percent change in average daily frequency (ADF) is calculated as absolute change in ADF divided by baseline ADF multiplied to 100. ADF is calculated as (number of seizures from central reader divided by stop date and time of EEG minus start date and time of EEG) multiplied to 60, multiplied to 24. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥1 month to <2 years
Number of subjects analysed	2 ^[3]
Units: Percent change
arithmetic mean (standard deviation)	99999 ( 99999 )

Notes
[3] - 99999 indicates that typical absence seizures data was not collected and analyzed.

No statistical analyses for this end point

Secondary: Absolute change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

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End point title

Absolute change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

End point description

Absolute change in ADF is calculated as the baseline ADF minus post-baseline ADF. ADF is calculated as (number of seizures from central reader divided by stop date and time of EEG minus start date and time of EEG) multiplied to 60, multiplied to 24. Full Analysis Set: all enrolled participants who took at least 1 dose of study drug in this Long-term study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed included all participants evaluable for this OM. Per planned analysis, participants were grouped as per cohort linked to source (DRC for ≥2 years /EEG for <2 years) from which their seizure data is recorded.

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422], or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥1 month to <2 years
Number of subjects analysed	2 ^[4]
Units: Seizure per day
arithmetic mean (standard deviation)	99999 ( 99999 )

Notes
[4] - 99999 indicates that typical absence seizures data was not collected and analyzed.

No statistical analyses for this end point

Secondary: 50% responder rate for total seizures (all types) in participants <2 years of age with Typical Absence Seizures (based on EEG data)

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End point title

50% responder rate for total seizures (all types) in participants <2 years of age with Typical Absence Seizures (based on EEG data)

End point description

End point type

Secondary

End point timeframe

From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)

End point values	Brivaracetam (BRV): Participants ≥1 month to <2 years
Number of subjects analysed	2 ^[5]
Units: Percentage of participants
number (not applicable)	99999

Notes
[5] - 99999 indicates that typical absence seizures data was not collected and analyzed.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline to end of Study (up to 10 years)

Adverse event reporting additional description

TEAEs are defined as AEs that had onset on or after the day of first BRV dose.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Age Cohort: ≥1 month to <2 years

Reporting group description

Participants from core study (LTFU [Long term follow-up] participants from N01263 [NCT00422422], EP0065 [NCT03405714] or N01349 [NCT03325439]) aged greater than or equal to (≥) 1 month to less than (<) 2 years entered evaluation period (EP) and received individualized Brivaracetam (BRV) dose as they were receiving at completion of core study. For all participants, the approximate BRV doses to be administered are 1 to 5 milligram per kilogram per day (mg/kg/day) (0.5, 1, 2, and 2.5 mg/kg twice daily[bid]), tablet or oral solution and can be up-titrated or down-titrated based on investigator decision with a maximum allowable BRV dose of 5.0 mg/kg/day (2.5 mg/kg bid), not to exceed a dose of 200 mg/day. The duration of the treatment for each participant was planned to be at least 3 years, until BRV received approval for pediatric participants in their age range or until the investigational medicinal product (IMP) development was stopped by the Sponsor.

Reporting group title

Age Cohort: ≥4 to <12 years

Reporting group description

Reporting group title

Age Cohort: ≥12 to <17 years

Reporting group description

Reporting group title

Age Cohort: ≥2 to <4 years

Reporting group description

Serious adverse events	Age Cohort: ≥1 month to <2 years	Age Cohort: ≥4 to <12 years	Age Cohort: ≥12 to <17 years	Age Cohort: ≥2 to <4 years
Total subjects affected by serious adverse events
subjects affected / exposed	14 / 36 (38.89%)	42 / 141 (29.79%)	19 / 65 (29.23%)	8 / 15 (53.33%)
number of deaths (all causes)	2	2	1	2
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma, low grade
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Circulatory collapse
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Haemodynamic instability
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Brain operation
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrostomy
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Osteotomy
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 36 (5.56%)	3 / 141 (2.13%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypothermia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inflammation
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device extrusion
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Testicular torsion
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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
Bronchospasm
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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 / 1
Respiratory distress
subjects affected / exposed	0 / 36 (0.00%)	2 / 141 (1.42%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Apnoea
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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 / 1
Aspiration
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Asthmatic crisis
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Chronic respiratory failure
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Affect lability
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aggression
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Anger
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Depression
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Homicidal ideation
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Suicide attempt
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Investigations
Blood bicarbonate decreased
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Hepatic enzyme increased
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Laparoscopy
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Weight decreased
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Injury, poisoning and procedural complications
Clavicle fracture
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Greenstick fracture
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Iatrogenic injury
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Toxicity to various agents
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Cryptorchism
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Developmental hip dysplasia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spina bifida
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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
Phimosis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Seizure
subjects affected / exposed	1 / 36 (2.78%)	12 / 141 (8.51%)	2 / 65 (3.08%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 6	1 / 20	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	2 / 36 (5.56%)	7 / 141 (4.96%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 12	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 36 (2.78%)	4 / 141 (2.84%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 7	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 / 36 (2.78%)	2 / 141 (1.42%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	0 / 36 (0.00%)	3 / 141 (2.13%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Complex partial seizures
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures with secondary generalisation
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Simple partial seizures
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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
Ataxia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydrocephalus
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Loss of consciousness
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Petit mal epilepsy
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Subdural hygroma
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune thrombocytopenic purpura
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Deafness neurosensory
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Vomiting
subjects affected / exposed	0 / 36 (0.00%)	3 / 141 (2.13%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	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 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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
Tooth deposit
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Toothache
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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
Volvulus
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Skin and subcutaneous tissue disorders
Skin reaction
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Chronic kidney disease
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Renal tubular acidosis
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Musculoskeletal and connective tissue disorders
Juvenile idiopathic arthritis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Scoliosis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	3 / 36 (8.33%)	4 / 141 (2.84%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 11	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 36 (2.78%)	3 / 141 (2.13%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Septic shock
subjects affected / exposed	0 / 36 (0.00%)	2 / 141 (1.42%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 36 (0.00%)	2 / 141 (1.42%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Corona virus infection
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neurocysticercosis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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 syncytial virus infection
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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 tract infection
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
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
Tuberculosis
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (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
Viral upper respiratory tract infection
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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 / 36 (2.78%)	3 / 141 (2.13%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperammonaemia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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
Hyponatraemia
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Underweight
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (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: 5%

Non-serious adverse events	Age Cohort: ≥1 month to <2 years	Age Cohort: ≥4 to <12 years	Age Cohort: ≥12 to <17 years	Age Cohort: ≥2 to <4 years
Total subjects affected by non serious adverse events
subjects affected / exposed	30 / 36 (83.33%)	120 / 141 (85.11%)	51 / 65 (78.46%)	13 / 15 (86.67%)
Vascular disorders
Hypotension
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	0	1
General disorders and administration site conditions
Device occlusion
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0	0
Fatigue
subjects affected / exposed	1 / 36 (2.78%)	5 / 141 (3.55%)	6 / 65 (9.23%)	2 / 15 (13.33%)
occurrences all number	1	6	10	3
Gait disturbance
subjects affected / exposed	2 / 36 (5.56%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	2	0	0
Pyrexia
subjects affected / exposed	15 / 36 (41.67%)	37 / 141 (26.24%)	7 / 65 (10.77%)	4 / 15 (26.67%)
occurrences all number	84	63	9	11
Influenza like illness
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Oedema peripheral
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 36 (0.00%)	2 / 141 (1.42%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	3	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	6 / 36 (16.67%)	19 / 141 (13.48%)	5 / 65 (7.69%)	2 / 15 (13.33%)
occurrences all number	8	26	8	4
Oropharyngeal pain
subjects affected / exposed	0 / 36 (0.00%)	6 / 141 (4.26%)	5 / 65 (7.69%)	2 / 15 (13.33%)
occurrences all number	0	7	7	2
Rhinitis allergic
subjects affected / exposed	2 / 36 (5.56%)	10 / 141 (7.09%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	5	11	0	0
Epistaxis
subjects affected / exposed	2 / 36 (5.56%)	6 / 141 (4.26%)	2 / 65 (3.08%)	1 / 15 (6.67%)
occurrences all number	2	8	2	1
Rhinorrhoea
subjects affected / exposed	4 / 36 (11.11%)	3 / 141 (2.13%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	18	4	1	0
Nasal congestion
subjects affected / exposed	1 / 36 (2.78%)	2 / 141 (1.42%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	1	3	1	1
Asthma
subjects affected / exposed	3 / 36 (8.33%)	0 / 141 (0.00%)	0 / 65 (0.00%)	2 / 15 (13.33%)
occurrences all number	5	0	0	2
Adenoidal hypertrophy
subjects affected / exposed	3 / 36 (8.33%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	1	0	0
Asthmatic crisis
subjects affected / exposed	2 / 36 (5.56%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	1	0	0
Bronchospasm
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	5	0	0	0
Aspiration
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Psychiatric disorders
Aggression
subjects affected / exposed	0 / 36 (0.00%)	14 / 141 (9.93%)	1 / 65 (1.54%)	2 / 15 (13.33%)
occurrences all number	0	18	1	2
Irritability
subjects affected / exposed	5 / 36 (13.89%)	14 / 141 (9.93%)	4 / 65 (6.15%)	0 / 15 (0.00%)
occurrences all number	8	15	4	0
Insomnia
subjects affected / exposed	2 / 36 (5.56%)	11 / 141 (7.80%)	0 / 65 (0.00%)	3 / 15 (20.00%)
occurrences all number	3	14	0	3
Suicidal ideation
subjects affected / exposed	0 / 36 (0.00%)	5 / 141 (3.55%)	4 / 65 (6.15%)	0 / 15 (0.00%)
occurrences all number	0	5	4	0
Anxiety
subjects affected / exposed	2 / 36 (5.56%)	4 / 141 (2.84%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences all number	2	5	2	0
Mental status changes
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	0	1
Hallucination, visual
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Investigations
Weight decreased
subjects affected / exposed	3 / 36 (8.33%)	10 / 141 (7.09%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences all number	3	13	2	0
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 36 (5.56%)	3 / 141 (2.13%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	2	3	1	0
Creatinine renal clearance decreased
subjects affected / exposed	2 / 36 (5.56%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	2	1	0	1
Injury, poisoning and procedural complications
Laceration
subjects affected / exposed	0 / 36 (0.00%)	4 / 141 (2.84%)	6 / 65 (9.23%)	0 / 15 (0.00%)
occurrences all number	0	6	10	0
Fall
subjects affected / exposed	1 / 36 (2.78%)	6 / 141 (4.26%)	8 / 65 (12.31%)	0 / 15 (0.00%)
occurrences all number	1	8	11	0
Congenital, familial and genetic disorders
Arnold-Chiari malformation
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Cardiac disorders
Atrioventricular block first degree
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	0 / 36 (0.00%)	21 / 141 (14.89%)	16 / 65 (24.62%)	1 / 15 (6.67%)
occurrences all number	0	58	75	1
Seizure
subjects affected / exposed	3 / 36 (8.33%)	17 / 141 (12.06%)	11 / 65 (16.92%)	2 / 15 (13.33%)
occurrences all number	9	29	17	2
Somnolence
subjects affected / exposed	3 / 36 (8.33%)	15 / 141 (10.64%)	5 / 65 (7.69%)	1 / 15 (6.67%)
occurrences all number	4	25	5	1
Complex partial seizures
subjects affected / exposed	3 / 36 (8.33%)	3 / 141 (2.13%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	3	3	1	0
Dizziness
subjects affected / exposed	0 / 36 (0.00%)	7 / 141 (4.96%)	8 / 65 (12.31%)	0 / 15 (0.00%)
occurrences all number	0	13	16	0
Partial seizures with secondary generalisation
subjects affected / exposed	0 / 36 (0.00%)	2 / 141 (1.42%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	0	2	1	1
Ataxia
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	0	1
Hypotonia
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	0	2
Muscle spasticity
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 36 (8.33%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	5	0	2	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 36 (0.00%)	6 / 141 (4.26%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	6	0	1
Eye disorders
Strabismus
subjects affected / exposed	2 / 36 (5.56%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	1	0	0
Eyelid oedema
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1	0	1
Hypermetropia
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0	0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	11 / 36 (30.56%)	34 / 141 (24.11%)	4 / 65 (6.15%)	5 / 15 (33.33%)
occurrences all number	19	61	4	6
Diarrhoea
subjects affected / exposed	7 / 36 (19.44%)	21 / 141 (14.89%)	8 / 65 (12.31%)	0 / 15 (0.00%)
occurrences all number	16	33	8	0
Abdominal pain
subjects affected / exposed	4 / 36 (11.11%)	12 / 141 (8.51%)	3 / 65 (4.62%)	0 / 15 (0.00%)
occurrences all number	4	20	9	0
Constipation
subjects affected / exposed	7 / 36 (19.44%)	10 / 141 (7.09%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences all number	11	12	4	0
Abdominal pain upper
subjects affected / exposed	1 / 36 (2.78%)	9 / 141 (6.38%)	8 / 65 (12.31%)	0 / 15 (0.00%)
occurrences all number	1	10	10	0
Nausea
subjects affected / exposed	4 / 36 (11.11%)	5 / 141 (3.55%)	3 / 65 (4.62%)	0 / 15 (0.00%)
occurrences all number	4	5	3	0
Gastrooesophageal reflux disease
subjects affected / exposed	5 / 36 (13.89%)	4 / 141 (2.84%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	6	5	0	1
Toothache
subjects affected / exposed	1 / 36 (2.78%)	5 / 141 (3.55%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	21	5	1	1
Abdominal distension
subjects affected / exposed	3 / 36 (8.33%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	5	1	0	0
Dysphagia
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	1	0	3
Enteritis
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	2	0	1	0
Teething
subjects affected / exposed	2 / 36 (5.56%)	1 / 141 (0.71%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	1	0	0
Hiatus hernia
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	0	1
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	2 / 36 (5.56%)	10 / 141 (7.09%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	2	15	1	0
Dermatitis contact
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	1	1	1	1
Dermatitis diaper
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	1	0	1
Alopecia
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0	0
Hair growth abnormal
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	2
Renal and urinary disorders
Urinary incontinence
subjects affected / exposed	0 / 36 (0.00%)	3 / 141 (2.13%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	10	0	1
Neurogenic bladder
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 36 (0.00%)	6 / 141 (4.26%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	0	6	1	1
Musculoskeletal and connective tissue disorders
Facial asymmetry
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Infections and infestations
Pharyngitis
subjects affected / exposed	10 / 36 (27.78%)	39 / 141 (27.66%)	8 / 65 (12.31%)	2 / 15 (13.33%)
occurrences all number	21	60	8	9
Upper respiratory tract infection
subjects affected / exposed	10 / 36 (27.78%)	23 / 141 (16.31%)	8 / 65 (12.31%)	5 / 15 (33.33%)
occurrences all number	19	38	12	15
Pharyngotonsillitis
subjects affected / exposed	5 / 36 (13.89%)	21 / 141 (14.89%)	10 / 65 (15.38%)	0 / 15 (0.00%)
occurrences all number	34	64	20	0
Gastroenteritis
subjects affected / exposed	8 / 36 (22.22%)	16 / 141 (11.35%)	5 / 65 (7.69%)	0 / 15 (0.00%)
occurrences all number	14	30	6	0
Influenza
subjects affected / exposed	5 / 36 (13.89%)	16 / 141 (11.35%)	6 / 65 (9.23%)	2 / 15 (13.33%)
occurrences all number	7	18	6	2
Bronchitis
subjects affected / exposed	7 / 36 (19.44%)	16 / 141 (11.35%)	1 / 65 (1.54%)	3 / 15 (20.00%)
occurrences all number	18	29	1	11
Rhinitis
subjects affected / exposed	5 / 36 (13.89%)	16 / 141 (11.35%)	2 / 65 (3.08%)	2 / 15 (13.33%)
occurrences all number	8	47	6	3
Nasopharyngitis
subjects affected / exposed	11 / 36 (30.56%)	44 / 141 (31.21%)	16 / 65 (24.62%)	4 / 15 (26.67%)
occurrences all number	44	114	41	6
Ear infection
subjects affected / exposed	2 / 36 (5.56%)	10 / 141 (7.09%)	4 / 65 (6.15%)	1 / 15 (6.67%)
occurrences all number	3	18	4	2
Tonsillitis
subjects affected / exposed	2 / 36 (5.56%)	13 / 141 (9.22%)	2 / 65 (3.08%)	1 / 15 (6.67%)
occurrences all number	2	21	3	1
Otitis media
subjects affected / exposed	4 / 36 (11.11%)	10 / 141 (7.09%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	13	24	0	1
Urinary tract infection
subjects affected / exposed	2 / 36 (5.56%)	6 / 141 (4.26%)	4 / 65 (6.15%)	3 / 15 (20.00%)
occurrences all number	3	11	5	3
Varicella
subjects affected / exposed	4 / 36 (11.11%)	9 / 141 (6.38%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	4	10	0	0
Pharyngitis streptococcal
subjects affected / exposed	2 / 36 (5.56%)	8 / 141 (5.67%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences all number	3	9	3	0
Viral infection
subjects affected / exposed	3 / 36 (8.33%)	7 / 141 (4.96%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	6	19	2	1
Conjunctivitis
subjects affected / exposed	5 / 36 (13.89%)	4 / 141 (2.84%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	6	5	1	2
Respiratory tract infection
subjects affected / exposed	3 / 36 (8.33%)	6 / 141 (4.26%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	3	11	1	37
Sinusitis
subjects affected / exposed	1 / 36 (2.78%)	7 / 141 (4.96%)	1 / 65 (1.54%)	2 / 15 (13.33%)
occurrences all number	3	12	1	2
Otitis media acute
subjects affected / exposed	3 / 36 (8.33%)	4 / 141 (2.84%)	2 / 65 (3.08%)	0 / 15 (0.00%)
occurrences all number	4	5	2	0
Pharyngitis bacterial
subjects affected / exposed	2 / 36 (5.56%)	4 / 141 (2.84%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	3	4	1	0
Viral pharyngitis
subjects affected / exposed	3 / 36 (8.33%)	3 / 141 (2.13%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	3	3	1	0
Gastroenteritis viral
subjects affected / exposed	0 / 36 (0.00%)	3 / 141 (2.13%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	0	3	1	1
Acute sinusitis
subjects affected / exposed	0 / 36 (0.00%)	3 / 141 (2.13%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	3	0	2
Lice infestation
subjects affected / exposed	1 / 36 (2.78%)	1 / 141 (0.71%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	1	1	1	1
Lower respiratory tract infection
subjects affected / exposed	3 / 36 (8.33%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	4	0	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 36 (0.00%)	1 / 141 (0.71%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1	0	1
Oral candidiasis
subjects affected / exposed	2 / 36 (5.56%)	0 / 141 (0.00%)	0 / 65 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0	0
Bacteraemia
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Gastroenteritis rotavirus
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Oral fungal infection
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Pneumonia
subjects affected / exposed	4 / 36 (11.11%)	9 / 141 (6.38%)	0 / 65 (0.00%)	4 / 15 (26.67%)
occurrences all number	4	11	0	16
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	6 / 36 (16.67%)	16 / 141 (11.35%)	7 / 65 (10.77%)	1 / 15 (6.67%)
occurrences all number	7	18	8	1
Metabolic acidosis
subjects affected / exposed	2 / 36 (5.56%)	1 / 141 (0.71%)	1 / 65 (1.54%)	0 / 15 (0.00%)
occurrences all number	2	1	1	0
Dehydration
subjects affected / exposed	1 / 36 (2.78%)	0 / 141 (0.00%)	1 / 65 (1.54%)	1 / 15 (6.67%)
occurrences all number	2	0	1	1
Hypercholesterolaemia
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Hyperlipidaemia
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Hypernatraemia
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Hyperuricaemia
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1
Underweight
subjects affected / exposed	0 / 36 (0.00%)	0 / 141 (0.00%)	0 / 65 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

26 Aug 2011

Protocol Amendment 1 was dated 26 Aug 2011 and the rationale was to include the Bayley Scales of Infant Development™, Second Edition (BSID-II™) in order to assess the cognitive development of children <18 months at Baseline in response to the European Pediatric Committee (PDCO) request. Withdrawal criteria were extended to include the consequences of any findings related to the results of liver function tests. Procedures for reporting serious adverse events (SAEs) were updated to implement the Food and Drug Administration (FDA) Final Rule requirements. The Columbia-Suicide Severity Rating Scale (C-SSRS) was added to address the request of the FDA that prospective assessments for suicidality are to be included in clinical studies involving all drugs for neurological indications. Some operational updates were also considered. Administrative changes included the update of the SAE reporting and CRO contact details. A few editorial changes were not listed in the specific changes section.

09 Dec 2011

Protocol Amendment 2 was dated 09 Dec 2011 and the rationale was to replace the children’s version of the C-SSRS with the version validated in multiple languages for study participants ≥6 years of age. The BSID-II score was replaced by the Bayley-III scales in order to apply the most recent version of the cognition scale. In addition, it was clarified that the cognition scale was to be used only in English-speaking countries, since it is validated only in English. The efficacy variables for study participants <2 years of age and for study participants with absence seizures were updated and amended in response to the PDCO requirements. It was clarified that safety laboratory assessments included hepatic monitoring. Furthermore, an error in the mathematical symbols used for the presentation of the age limits of the EEG assessments was corrected, and the SAE reporting details were updated. Administrative changes included the update of the Clinical Project Manager contact details and typographical corrections. A few editorial changes were additionally listed in the specific changes section.

26 Sep 2012

Protocol Amendment 3 was dated 26 Sep 2012 and the rationale was to allow study participants who had not previously participated in a clinical study of BRV to enroll directly into N01266 (ie, DE study participants). Up to 100 study participants who were ≥4 years to <17 years of age with POS and met entry criteria were planned for direct enrollment, and overall planned enrollment increased from up to 500 study participants to up to 600 study participants. The purpose of direct enrollment was to obtain sufficient long-term safety exposure data in study participants ≥4 years to <17 years of age. With this amendment, the BRIEF-P/BRIEF and PedsQL were added to the assessments for study participants ≥2 years of age. These assessments were added to provide an additional means of assessing the effect of BRV on cognition and quality of life, respectively, in pediatric study participants ≥2 years of age.

10 Dec 2013

Protocol Amendment 4 was dated 10 Dec 2013. As a result of the PK analyses performed on the plasma samples collected at N01263 completion, the plasma concentrations approximating the concentrations for adults receiving BRV 200mg/day were not achieved by the dosing scheme initially included in N01266. Thus, N01266 was amended to allow a maximum BRV dose of 5.0mg/kg/day (not to exceed a total dose of BRV 200mg/day) for all study participants, irrespective of age. The number of DE study participants was increased from “up to” to “at least” 100 study participants with the planned total enrollment of approximately 600 study participants to allow flexibility in the number of study participants reaching 1 year of exposure. Demographics and childbearing potential were captured at the EV for LTFU study participants, instead of using the data recorded from either the Baseline or the FV of the core study. The handling of protocol deviations was made consistent with the updated statistical analysis process. In addition, it was clarified that although no formal interim analysis was planned, the data may be reported prior to the completion of this study to support ongoing data cleaning, annual reports, regulatory submissions, and publications.

14 Dec 2016

Protocol Amendment 5 was dated 14 Dec 2016. The rationale for this amendment was to: • Add an updated list of Anticipated SAEs. • Add a section on adverse events (AEs) of special interest in accordance with the Sponsor template requirement. • Update the schema for down-titration to align with N01263 and provide uniformity across the BRV pediatric development program. • Remove the requirement that study participants <7 years of age receive oral solution and, as appropriate, study participants ≥7 years of age receive tablets in recognition of individual study participant preferences to allow study participants additional flexibility in treatment options. • Provide EV information specific to study participants who enroll from core studies under development. • Provide additional clarity regarding enrolled study participants who participate in EP0065 and then resume participation in N01266. Protocol Amendment 3 had allowed for study participants to participate in what was called a “substudy.” • Clarify the requirement that study participants ≥2 years of age with typical absence seizures have at least a 24-hour EEG, instead of a 1-hour EEG. • Eliminate the EEG at the 3-month visit (Visit 4) and the requirement for study participants to have EEGs after they reach 2 years of age (exception: study participants with typical absence seizures), and allow the EDV EEGs to be done at the Investigator’s discretion. This change was made due to the limited clinical utility of these assessments and to unburden the Investigator, study participant, and study participant’s caregiver/family. • Replace serum pregnancy tests with urine pregnancy tests and include urine pregnancy tests at all MEVs.

14 Dec 2016

Protocol Amendment 5 Continued: • Update according to the current Sponsor protocol template. This included: − The addition of text regarding potential drug-induced liver injury (PDILI); these changes were strictly template-driven. They did not reflect a change in the liver safety signal for BRV and were included only for alignment with updated standard Sponsor text across programs. − The streamlining of the Introduction with reference to the availability of additional information in the Investigator’s Brochure. • Update of the Introduction text to include more current literature references and to include information about the marketing authorization of BRV. • Revise the duration of the study for an individual study participant from approximately 3 years to at least 3 years, with the addition of the possibility of study participants entering a managed access program, if available. • Remove the BRV 1.0mg/mL oral solution from the description of the IMP as the BRV 10mg/mL oral solution is adequate for dosing.

06 Mar 2018

Protocol Amendment 6 was dated 06 Mar 2018 and the rationale was to: • Update language for Bayley-III scales to include countries where a validated translation was available. • Remove reference to central reading of EEGs to provide flexibility. • Remove EEG assessment for the EV (all study participants). • Update inclusion criteria to align language enhancements provided in country-specific amendment (Czech Republic) (ie, diagnosis of epilepsy and contraceptive language). • Update language in regards to partner pregnancy to align with Sponsor’s Standard Operating Procedure (SOP) and protocol templates. • Add blood draw volumes for study participants <2 years of age. • Clarify PedsQL age range (≥2 years of age) as this assessment is not used in children <2 years of age. • Clarify for all other EEGs (ie, Visit 5 and yearly thereafter) the duration in study participants >2 years of age.

18 Apr 2019

Protocol Amendment 7 was dated 18 Apr 2019. This amendment was implemented to update the pregnancy text to clarify that the Pregnancy Report and Outcome form is to be completed for all pregnancies.

25 Jun 2020

Protocol Amendment 8 was dated 25 Jun 2020. This amendment was implemented to: • Reorganize the study variables into primary, secondary, other variables in compliance with reporting agencies. This change does not affect the type or processing of data collected and reported in the study report, as they will be assessed as initially planned. • Allow study participants to transition to another BRV study. • Add information regarding down-titration for study participants who do not continue BRV treatment after completing the study. • Clarify the text describing the maximum dose of BRV. • Modify the study conduct to ensure the safety of participants in response to the COVID-19 pandemic.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results:
Open-Label, Single-Arm, Multicenter, Long-Term Study to Evaluate Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Pediatric Subjects with Epilepsy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study

Primary: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study

Primary: Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study

Primary: Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study

Secondary: Absolute change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on daily record card [DRC])

Secondary: Absolute change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on daily record card [DRC])

Secondary: Percent change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on DRC data)

Secondary: Percent change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on DRC data)

Secondary: 50% responder rate for participants ≥2 years of age for total seizures (all types) (based on DRC data)

Secondary: 50% responder rate for participants ≥2 years of age for total seizures (all types) (based on DRC data)

Secondary: Absolute change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: Absolute change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: 50% responder rate for participants <2 years of age for total seizures (all types) (based on EEG data)

Secondary: 50% responder rate for participants <2 years of age for total seizures (all types) (based on EEG data)

Secondary: Percent change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: Percent change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: Absolute change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: Absolute change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: 50% responder rate for total seizures (all types) in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: 50% responder rate for total seizures (all types) in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
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Greece
Hungary
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Italy
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Luxembourg
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Outside EU/EEA

Clinical trials

Clinical Trial Results: Open-Label, Single-Arm, Multicenter, Long-Term Study to Evaluate Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Pediatric Subjects with Epilepsy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study

Primary: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study

Primary: Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study

Primary: Percentage of participants with treatment-emergent serious adverse events (SAEs) during the study

Secondary: Absolute change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on daily record card [DRC])

Secondary: Absolute change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on daily record card [DRC])

Secondary: Percent change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on DRC data)

Secondary: Percent change in 28-days adjusted partial-onset-seizure (POS) frequency for participants aged ≥2 years from Baseline to the end of the evaluation period in participants with POS only (based on DRC data)

Secondary: 50% responder rate for participants ≥2 years of age for total seizures (all types) (based on DRC data)

Secondary: 50% responder rate for participants ≥2 years of age for total seizures (all types) (based on DRC data)

Secondary: Absolute change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: Absolute change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in participants <2 years of age with POS only (based on EEG data)

Secondary: 50% responder rate for participants <2 years of age for total seizures (all types) (based on EEG data)

Secondary: 50% responder rate for participants <2 years of age for total seizures (all types) (based on EEG data)

Secondary: Percent change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: Percent change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: Absolute change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: Absolute change in average daily frequency of POS in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: 50% responder rate for total seizures (all types) in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Secondary: 50% responder rate for total seizures (all types) in participants <2 years of age with Typical Absence Seizures (based on EEG data)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Open-Label, Single-Arm, Multicenter, Long-Term Study to Evaluate Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Pediatric Subjects with Epilepsy