Open-label Long-term Study of Adjunctive Brivaracetam in... | NCT01364597

ID	Type	Description	Link
2011-000374-60	EudraCT Number

Label	Type	Description	Intervention Names
Brivaracetam	Experimental		Drug: Brivaracetam (BRV)

Name	Type	Description	Arm Group Labels	Other Names
Brivaracetam (BRV)	Drug	The max BRV dose will be 5.0 mg/kg/day, not to exceed a dose of 200 mg/day for subjects with body weight >40kg. Subjects may receive oral solution or oral tablets. The LTFU subjects will start dosing in N01266 on the individualized BRV dose they were receiving at the completion of the core study. Subjects must be able to tolerate the min BRV dose specified in the core study to be eligible for entry into the Evaluation Period of N01266. Dose can be adjusted as considered necessary by the Investigator and required by the subject's medical condition. All subjects who prematurely discontinue the study should complete an EDV and have their BRV dose down titrated by a maximum of half the dose every week for a maximum of 4 weeks until a dose of 1 mg/kg/day (50 mg/day for subjects with body weights >50kg) is reached.

Measure	Description	Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study	TEAEs are defined as AEs that had onset on or after the day of first BRV dose.	From Baseline to end of study (up to 10 years)
Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Study	TEAEs are defined as AEs that had onset on or after the day of first BRV dose. A SAE was defined as an event that met 1 or more of the below criteria: a) Death, b) Life-threatening, (Life-threatening did not include a reaction that might have caused death had it occurred in a more severe form.) c) Significant or persistent disability/incapacity, d) Congenital anomaly/birth defect (including that occurring in a fetus), e) Important medical event that, based upon appropriate medical judgment, may have jeopardized participant and may have required medical or surgical intervention to prevent 1 of the other outcomes listed in the 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. (A participant admitted to a hospital, even if released on the same day, met the criteria for the initial inpatient hospitalization).	From Baseline to end of study (up to 10 years)

Measure	Description	Time Frame
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])	Absolute change in seizure frequency per 28 days based on the daily record card (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 the number of partial seizures by the number of days for which the diary was completed, and multiplying the resulting value by 28. This OM was analyzed in participants ≥2 years (per DRC data) only. Here in the study FAS indicates Full Analysis Set, EEG indicates electroencephalogram, OM indicates Outcome measure

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

All Subjects:

Informed Consent form (ICF) is signed and dated by the parent(s) or legal representative(s)
Subject/legal representative is considered reliable and capable of adhering to the protocol
For female subjects:
Subject is not of childbearing potential

OR if women of childbearing potential, and sexually active only if:

Adequate Contraceptive method
Negative pregnancy test
Understands the consequences and potential risks of inadequately protected sexual activity, understands and properly uses contraceptive methods, and is willing to inform the Investigator of any contraception changes

Long Term Follow-up Subjects:

- Male or female subjects having participated in a core study with a confirmed diagnosis of epilepsy and for whom a reasonable benefit from long-term administration of BRV is expected

Directly Enrolled Subjects:

Subject is a male or female ≥4 years to <17 years of age
Subject has a clinical diagnosis of partial-onset seizures (POS) according to the International League Against Epilepsy (ILAE) classification
Subject has an EEG compatible with the clinical diagnosis of POS
Subject has been observed to have uncontrolled POS after an adequate course of treatment (in the opinion of the Investigator) with at least 1 antiepileptic drug (AED; concurrently or sequentially)
Subject had at least 1 seizure (POS) during the 3 weeks before the Screening Visit (ScrV)
Subject is taking at least 1 AED. All AEDs need to be at a stable dose for at least 7 days before the ScrV. Vagal nerve stimulator stable for at least 2 weeks before the ScrV is allowed and will be counted as a concomitant AED. Benzodiazepines taken more than once a week (for any indication) will be considered as a concomitant AED

Exclusion Criteria:

All Subjects:

Subject is a pregnant or nursing female
Subject has severe medical, neurological, or psychiatric disorders or laboratory values, which may have an impact on the safety of the subject.
Subject has planned participation in any clinical study of another investigational drug or device.
Subject has >1.5x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >1.0xULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35%). N01349 subjects with a total bilirubin > ULN may be considered for the study if benign unconjugated hyperbilirubinemia is suspected in the context of prolonged neonatal jaundice, after discussion with the medical monitor. For randomized subjects with a baseline result >ULN for ALT, AST, ALP, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the eCRF. If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at the baseline referenced in Table 5-1 for LTFU subjects and at the Screening Visit for directly enrolled subjects, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject must be discussed with the Medical Monitor. Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation. This includes re-screening.
Subject has chronic liver disease.

Long Term Follow-up Subjects:

Subject had hypersensitivity to BRV or excipients or comparative drugs as stated in this protocol during the course of the core study.
Subject had poor compliance with the visit schedule or medication intake in the core study.
Subject ≥6 years of age has a lifetime history of suicide attempt (including actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the EV. If a subject has active suicidal ideation without a specific plan as indicated by a positive response ("Yes") to Question 4 of Columbia-Suicide Severity Rating Scale (C SSRS) at the EV, the subject should be referred immediately to a Mental Healthcare Professional and may be excluded from the study based upon the Investigator's judgment of benefit/risk of continuing the subject in the study/on study medication.

Directly Enrolled Subjects:

Subject has previously received BRV.
Subject had concomitant use of LEV at the ScrV. In addition, the use of LEV is prohibited for at least 4 weeks prior to the ScrV.
Subject has epilepsy secondary to a progressive cerebral disease or tumor, or any other progressively neurodegenerative disease. Stable arteriovenous malformations, meningiomas or other benign tumors may be acceptable according to Investigator's opinion.
Subject has a history of primary generalized epilepsy.
Subject has a history of status epilepticus in the month immediately prior to the ScrV or during the Up Titration Period.
Subject has a history or presence of pseudoseizures.
Subject is suffering only from febrile seizures.
Subject is on felbamate with less than 18 months continuous exposure. Subject who has taken felbamate for a combined duration of treatment and wash out of <18 months before the ScrV.
Subjects treated with vigabatrin who have visual field defects.
Subject has an allergy to pyrrolidone derivatives or investigational product excipients or a history of multiple drug allergies.
Subject has any clinically significant acute or chronic illness as determined during the physical examination or from other information available to the Investigator (eg, bone marrow depression, chronic hepatic disease, severe renal impairment, psychiatric disorder).
Subject has an underlying disease or is receiving a treatment that may interfere with the absorption, distribution, metabolism, and elimination of the study drug.
Subject has any medical condition that might interfere with his/her study participation (eg, serious infection or scheduled elective surgery).
Subject has a terminal illness.
Subject has any clinically significant deviations from reference range values for laboratory parameters as determined by the Investigator.
Subject has a clinically relevant ECG abnormality according to the Investigator.
Subject had major surgery within 6 months prior to the ScrV.
Subject received any investigational drug or device within the 30 days prior to the ScrV.

Name	Affiliation	Role
UCB Cares	+1 877 822 9493 (UCB)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
N01266 243		Los Angeles	California	90027	United States
N01266 108

PubMed Identifier	Type	Citation	Retractions
37597326	Result	Lagae L, Klotz KA, Fogarasi A, Floricel F, Reichel C, Elshoff JP, Fleyshman S, Kang H. Long-term safety and efficacy of adjunctive brivaracetam in pediatric patients with epilepsy: An open-label, follow-up trial. Epilepsia. 2023 Nov;64(11):2934-2946. doi: 10.1111/epi.17754. Epub 2023 Sep 5.
40737960	Result	Bourikas D, Elmoufti S, Elshoff JP, Little A, Pucylowski K, Moseley B, Lagae L. Long-term tolerability and efficacy of adjunctive brivaracetam in pediatric patients with generalized-onset seizures: Subgroup analysis of an open-label, follow-up trial. Epilepsy Behav. 2025 Oct;171:110569. doi: 10.1016/j.yebeh.2025.110569. Epub 2025 Jul 29.

Label	URL
Product Information	View source

ID	Title	Description
FG000	Age Cohort: ≥1 Month to <2 Years	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 25, 2020	Jul 28, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Age Cohort: ≥1 Month to <2 Years	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.
OG001	Age Cohort: ≥2 to <4 Years	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.
OG002	Age Cohort: ≥4 to <12 Years	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.
OG003	Age Cohort: ≥12 to <17 Years	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.

Units	Counts
Participants	OG00036 OG00115 OG002141 OG003

Title

Denominators

Categories

Title	Measurements
	OG00094.4 OG00193.3 OG00293.6 OG003

Primary

Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Study

TEAEs are defined as AEs that had onset on or after the day of first BRV dose. A SAE was defined as an event that met 1 or more of the below criteria: a) Death, b) Life-threatening, (Life-threatening did not include a reaction that might have caused death had it occurred in a more severe form.) c) Significant or persistent disability/incapacity, d) Congenital anomaly/birth defect (including that occurring in a fetus), e) Important medical event that, based upon appropriate medical judgment, may have jeopardized participant and may have required medical or surgical intervention to prevent 1 of the other outcomes listed in the 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. (A participant admitted to a hospital, even if released on the same day, met the criteria for the initial inpatient hospitalization).

The Safety Set (SS) consisted of all enrolled participants who took at least 1 dose of study medication.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Age Cohort: ≥1 Month to <2 Years	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.

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])

Absolute change in seizure frequency per 28 days based on the daily record card (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 the number of partial seizures by the number of days for which the diary was completed, and multiplying the resulting value by 28. This OM was analyzed in participants ≥2 years (per DRC data) only.

Here in the study FAS indicates Full Analysis Set, EEG indicates electroencephalogram, OM indicates Outcome measure

FAS: enrolled participants who had at least 1 dose of study drug in the study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed consist of all participants (≥2 years only [per DRC data]) evaluable for this OM and it differs in absolute and percent change OMs as later cannot be analyzed with 0 baseline ADF. Per plan, participants were grouped per cohort linked to source (DRC for ≥2 years/EEG for <2 years) from which their seizure data is recorded.

Posted

Mean

Standard Deviation

seizure frequency per 28-days

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥ 2 Years to <17 Years	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.

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)

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. This OM was analyzed in participants ≥2 years (per DRC data) only.

Posted

Mean

Standard Deviation

percent change

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥ 2 Years to <17 Years	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.

Secondary

50% Responder Rate for Participants ≥2 Years of Age for Total Seizures (All Types) (Based on DRC Data)

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. This OM was analyzed in participants ≥2 years (per DRC data) only.

FAS: 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 of age (per DRC data) only.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥2 Years to <17 Years	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.

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)

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. This OM was analyzed in participants <2 years (per EEG data) only.

FAS: enrolled participants who had at least 1 dose of study drug in the study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed consist of all participants (<2 years only [per EEG data]) evaluable for this OM and it differs in absolute and percent change OMs as later cannot be analyzed with 0 baseline ADF. Per plan, participants were grouped per cohort linked to source (DRC for ≥2 years/EEG for <2 years) from which their seizure data is recorded.

Posted

Mean

Standard Deviation

seizures per day

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥1 Month to <2 Years	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.

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)

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. This OM was analyzed in participants <2 years (per EEG data) only.

FAS: enrolled participants who had at least 1 dose of study drug in the study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed consist of all participants (<2 years only [per EEG data]) evaluable for this OM and it differs in absolute and percent change OMs as later cannot be analyzed with 0 baseline ADF. Per plan, participants were grouped per cohort linked to source (DRC for ≥2 years/EEG for <2 years) from which their seizure data is recorded.

Posted

Mean

Standard Deviation

percent change

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥1 Month to <2 Years	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.

Secondary

50% Responder Rate for Participants <2 Years of Age for Total Seizures (All Types) (Based on EEG Data)

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. This OM was analyzed in participants <2 years (per EEG data) only.

FAS: enrolled participants who had at least 1 dose of study drug in the study and had at least 1 completed post-baseline DRC or EEG. Overall number of participants analyzed consist of all participants (<2 years only [per EEG data]) evaluable for this OM. Per plan, participants were grouped per cohort linked to source (DRC for ≥2 years/EEG for <2 years) from which their seizure data is recorded.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥1 Month to <2 Years	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.

Secondary

Absolute Change in Average Daily Frequency of POS in Participants <2 Years of Age With Typical Absence Seizures (Based on EEG Data)

Typical absence seizures data was not collected and analyzed.

Posted

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥1 Month to <2 Years	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.

Secondary

Percent Change in Average Daily Frequency of POS in Participants <2 Years of Age With Typical Absence Seizures (Based on EEG Data)

Typical absence seizures data was not collected and analyzed.

Posted

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥1 Month to <2 Years	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.

Secondary

50% Responder Rate for Total Seizures (All Types) in Participants <2 Years of Age With Typical Absence Seizures (Based on EEG Data)

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.

Typical absence seizures data was not collected and analyzed.

Posted

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

ID	Title	Description
OG000	Brivaracetam (BRV): Participants ≥1 Month to <2 Years	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.

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG0030 events0 affected65 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Cryptorchism	Congenital, familial and genetic disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Developmental hip dysplasia	Congenital, familial and genetic disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Spina bifida	Congenital, familial and genetic disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Phimosis	Congenital, familial and genetic disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Deafness neurosensory	Ear and labyrinth disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0023 events3 affected141 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Faecaloma	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Tooth deposit	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Volvulus	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0011 events1 affected15 at risk EG0023 events3 affected141 at risk EG003
Asthenia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hypothermia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Inflammation	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0006 events3 affected36 at risk EG0010 events0 affected15 at risk EG00211 events4 affected141 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0023 events3 affected141 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Septic shock	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0022 events2 affected141 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0022 events2 affected141 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Viral infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Appendicitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Corona virus infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Epididymitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Neurocysticercosis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Periorbital cellulitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Respiratory syncytial virus infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Tuberculosis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Greenstick fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Iatrogenic injury	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Laparoscopy	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Weight decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0023 events3 affected141 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hyperammonaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Underweight	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Juvenile idiopathic arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0022 events1 affected141 at risk EG003
Scoliosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Astrocytoma, low grade	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Seizure	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 events1 affected36 at risk EG0011 events1 affected15 at risk EG00220 events12 affected141 at risk EG003
Status epilepticus	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0010 events0 affected15 at risk EG00212 events7 affected141 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0027 events4 affected141 at risk EG003
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0022 events2 affected141 at risk EG003
Somnolence	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0024 events3 affected141 at risk EG003
Complex partial seizures	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Simple partial seizures	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Ataxia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hydrocephalus	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Petit mal epilepsy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Subdural hygroma	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Affect lability	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Aggression	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Anger	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Depression	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Homicidal ideation	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Renal tubular acidosis	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Testicular torsion	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0023 events2 affected141 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Apnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Brain operation	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Gastrostomy	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0002 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Osteotomy	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Circulatory collapse	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Haemodynamic instability	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Device extrusion	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 events3 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG0032 events1 affected65 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Arnold-Chiari malformation	Congenital, familial and genetic disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0026 events6 affected141 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0026 events6 affected141 at risk EG003
Strabismus	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Eyelid oedema	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Hypermetropia	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00019 events11 affected36 at risk EG0016 events5 affected15 at risk EG00261 events34 affected141 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00016 events7 affected36 at risk EG0010 events0 affected15 at risk EG00233 events21 affected141 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 events4 affected36 at risk EG0010 events0 affected15 at risk EG00220 events12 affected141 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 events7 affected36 at risk EG0010 events0 affected15 at risk EG00212 events10 affected141 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG00210 events9 affected141 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 events4 affected36 at risk EG0010 events0 affected15 at risk EG0025 events5 affected141 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 events5 affected36 at risk EG0011 events1 affected15 at risk EG0025 events4 affected141 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00021 events1 affected36 at risk EG0011 events1 affected15 at risk EG0025 events5 affected141 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 events3 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0013 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Teething	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Device occlusion	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0013 events2 affected15 at risk EG0026 events5 affected141 at risk EG003
Gait disturbance	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0022 events1 affected141 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00084 events15 affected36 at risk EG00111 events4 affected15 at risk EG00263 events37 affected141 at risk EG003
Influenza like illness	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0023 events2 affected141 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00021 events10 affected36 at risk EG0019 events2 affected15 at risk EG00260 events39 affected141 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00019 events10 affected36 at risk EG00115 events5 affected15 at risk EG00238 events23 affected141 at risk EG003
Pharyngotonsillitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00034 events5 affected36 at risk EG0010 events0 affected15 at risk EG00264 events21 affected141 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00014 events8 affected36 at risk EG0010 events0 affected15 at risk EG00230 events16 affected141 at risk EG003
Influenza	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0007 events5 affected36 at risk EG0012 events2 affected15 at risk EG00218 events16 affected141 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00018 events7 affected36 at risk EG00111 events3 affected15 at risk EG00229 events16 affected141 at risk EG003
Rhinitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0008 events5 affected36 at risk EG0013 events2 affected15 at risk EG00247 events16 affected141 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00044 events11 affected36 at risk EG0016 events4 affected15 at risk EG002114 events44 affected141 at risk EG003
Ear infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0012 events1 affected15 at risk EG00218 events10 affected141 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected15 at risk EG00221 events13 affected141 at risk EG003
Otitis media	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00013 events4 affected36 at risk EG0011 events1 affected15 at risk EG00224 events10 affected141 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0013 events3 affected15 at risk EG00211 events6 affected141 at risk EG003
Varicella	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0004 events4 affected36 at risk EG0010 events0 affected15 at risk EG00210 events9 affected141 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0010 events0 affected15 at risk EG0029 events8 affected141 at risk EG003
Viral infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0006 events3 affected36 at risk EG0011 events1 affected15 at risk EG00219 events7 affected141 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0006 events5 affected36 at risk EG0012 events1 affected15 at risk EG0025 events4 affected141 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events3 affected36 at risk EG00137 events1 affected15 at risk EG00211 events6 affected141 at risk EG003
Sinusitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events1 affected36 at risk EG0012 events2 affected15 at risk EG00212 events7 affected141 at risk EG003
Otitis media acute	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0004 events3 affected36 at risk EG0010 events0 affected15 at risk EG0025 events4 affected141 at risk EG003
Pharyngitis bacterial	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0010 events0 affected15 at risk EG0024 events4 affected141 at risk EG003
Viral pharyngitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected15 at risk EG0023 events3 affected141 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0023 events3 affected141 at risk EG003
Acute sinusitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events1 affected15 at risk EG0023 events3 affected141 at risk EG003
Lice infestation	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0004 events3 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Hand-foot-and-mouth disease	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Gastroenteritis rotavirus	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Oral fungal infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0004 events4 affected36 at risk EG00116 events4 affected15 at risk EG00211 events9 affected141 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0026 events4 affected141 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected15 at risk EG0028 events6 affected141 at risk EG003
Weight decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected15 at risk EG00213 events10 affected141 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0023 events3 affected141 at risk EG003
Creatinine renal clearance decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 events6 affected36 at risk EG0011 events1 affected15 at risk EG00218 events16 affected141 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events1 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Underweight	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Facial asymmetry	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG00258 events21 affected141 at risk EG003
Seizure	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0009 events3 affected36 at risk EG0012 events2 affected15 at risk EG00229 events17 affected141 at risk EG003
Somnolence	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 events3 affected36 at risk EG0011 events1 affected15 at risk EG00225 events15 affected141 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG00213 events7 affected141 at risk EG003
Complex partial seizures	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected15 at risk EG0023 events3 affected141 at risk EG003
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0022 events2 affected141 at risk EG003
Ataxia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hypotonia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0012 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Muscle spasticity	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Irritability	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0008 events5 affected36 at risk EG0010 events0 affected15 at risk EG00215 events14 affected141 at risk EG003
Aggression	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected15 at risk EG00218 events14 affected141 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0013 events3 affected15 at risk EG00214 events11 affected141 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected15 at risk EG0025 events5 affected141 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0025 events4 affected141 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hallucination, visual	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG00210 events3 affected141 at risk EG003
Neurogenic bladder	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0008 events6 affected36 at risk EG0014 events2 affected15 at risk EG00226 events19 affected141 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected15 at risk EG0027 events6 affected141 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 events2 affected36 at risk EG0010 events0 affected15 at risk EG00211 events10 affected141 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected15 at risk EG0028 events6 affected141 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00018 events4 affected36 at risk EG0010 events0 affected15 at risk EG0024 events3 affected141 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 events3 affected36 at risk EG0012 events2 affected15 at risk EG0020 events0 affected141 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0023 events2 affected141 at risk EG003
Adenoidal hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG0021 events1 affected141 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected15 at risk EG00215 events10 affected141 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0021 events1 affected141 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0010 events0 affected15 at risk EG0020 events0 affected141 at risk EG003
Hair growth abnormal	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events1 affected15 at risk EG0020 events0 affected141 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected15 at risk EG0020 events0 affected141 at risk EG003

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Title	Description
BG000	Age Cohort: ≥1 Month to <2 Years	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.
BG001	Age Cohort: ≥2 to <4 Years	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.
BG002	Age Cohort: ≥4 to <12 Years	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.
BG003	Age Cohort: ≥12 to <17 Years	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.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Age Cohort: ≥1 Month to <2 Years	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.	2	36	14	36	30	36
EG001	Age Cohort: ≥2 to <4 Years	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.	2	15	8	15	13	15
EG002	Age Cohort: ≥4 to <12 Years	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.	2	141	42	141	120	141
EG003	Age Cohort: ≥12 to <17 Years	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.	1	65	19	65	51	65