Trial Outcomes & Findings for Study to Look at How Effective Briviact is as add-on Treatment for Patients With Epilepsy With Partial Onset Seizures (NCT NCT02687711)

NCT ID: NCT02687711

Last Updated: 2021-08-04

Results Overview

Participants who remained in the study and were on BRV treatment for at least 1 year (\>=330 days) after their start of BRV were classed as having 12 months of treatment retention.

• Recruitment status: COMPLETED
• Target enrollment: 544 participants
• Primary outcome timeframe: Month 12 (end of Observation Period)
• Results posted on: 2021-08-04

Participant Flow

The study started to enroll participants in February 2016 and concluded in July 2020.

Participant Flow refers to the Safety Set.

Participant milestones

Measure	Brivaracetam (BRV) Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC).
Overall Study STARTED	544
Overall Study COMPLETED	332
Overall Study NOT COMPLETED	212

Reasons for withdrawal

Measure	Brivaracetam (BRV) Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC).
Overall Study Adverse Event	89
Overall Study Lack of Efficacy	70
Overall Study Lost to Follow-up	20
Overall Study Consent withdrawn	15
Overall Study Participant moved to another country and continued treatment for epilepsy in that country	1
Overall Study Too expensive	4
Overall Study Participant moved abroad	1
Overall Study Progression of other medical condition (dementia, pneumonia)	1
Overall Study Perceived increase in seizures but diary records show no increase compared to pre-study	1
Overall Study Disliked taste	1
Overall Study Low mood	1
Overall Study Side effects	1
Overall Study Change of Hospital	1
Overall Study Liver Encephalopathy	1
Overall Study Participant experience side effects, fatigue. Most likely not related to investigational product	1
Overall Study Withdrawn due to intake interruption	1
Overall Study Stopped in preparation for epilepsy surgery	1
Overall Study Diagnosis epilepsy revised to psychogenic seizures	1
Overall Study Participant was not able to come in our clinic because participant could not find a car driver	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Brivaracetam (BRV) n=544 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC).
Age, Categorical <=18 years	8 Participants n=544 Participants
Age, Categorical Between 18 and 65 years	492 Participants n=544 Participants
Age, Categorical >=65 years	44 Participants n=544 Participants
Age, Continuous	43.6 years STANDARD_DEVIATION 14.1 • n=544 Participants
Sex: Female, Male Female	287 Participants n=544 Participants
Sex: Female, Male Male	257 Participants n=544 Participants

PRIMARY outcome

Timeframe: Month 12 (end of Observation Period)

Population: The Full Analysis Set (FAS) was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this non interventional study (NIS).

Participants who remained in the study and were on BRV treatment for at least 1 year (>=330 days) after their start of BRV were classed as having 12 months of treatment retention.

Outcome measures

Measure	Brivaracetam (FAS) n=541 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percentage of Participants Remaining in the Study and on BRV Treatment at Month 12	57.7 percentage of participants Interval 53.4 to 61.9

SECONDARY outcome

Timeframe: Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS.

Participants who remained in the study and were on BRV treatment for at least 3 months (>=90 days) after first BRV administration were classed as having 3 months of treatment retention.

Outcome measures

Measure	Brivaracetam (FAS) n=541 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percentage of Participants Remaining in the Study and on BRV Treatment at Month 3	82.4 percentage of participants Interval 79.0 to 85.6

SECONDARY outcome

Timeframe: Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS.

Participants who remained in the study and were on BRV treatment for at least 6 months (>=180 days) after first BRV administration were classed as having 6 months of treatment retention.

Outcome measures

Measure	Brivaracetam (FAS) n=541 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percentage of Participants Remaining in the Study and on BRV Treatment at Month 6	70.6 percentage of participants Interval 66.6 to 74.4

SECONDARY outcome

Timeframe: From Baseline (Day 1) to Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Absolute change in POS frequency was defined as: 28-day Baseline - 28-day post-Baseline seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=398 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Absolute Change in Partial-onset Seizure (POS) Frequency From Baseline to Month 3	4.54 seizures per 28 days Standard Deviation 24.34

SECONDARY outcome

Timeframe: From Baseline (Day 1) to Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Absolute change in POS frequency was defined as: 28-day Baseline - 28-day post-Baseline seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=343 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Absolute Change in Partial-onset Seizure (POS) Frequency From Baseline to Month 6	3.29 seizures per 28 days Standard Deviation 16.92

SECONDARY outcome

Timeframe: From Baseline (Day 1) to Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Absolute change in POS frequency was defined as: 28-day Baseline - 28-day post-Baseline seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=259 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Absolute Change in Partial-onset Seizure (POS) Frequency From Baseline to Month 12	3.75 seizures per 28 days Standard Deviation 16.05

SECONDARY outcome

Timeframe: From Baseline (Day 1) to end of Observation Period (up to Month 12/withdrawal)

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment and were classified as study completers or who withdrew early.

Absolute change in POS frequency was defined as: 28-day Baseline - 28-day post-Baseline seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=373 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Absolute Change in Partial-onset Seizure (POS) Frequency From Baseline to End of Observation Period	1.69 seizures per 28 days Standard Deviation 26.59

SECONDARY outcome

Timeframe: From Baseline (Day 1) to Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Percent change in POS frequency was defined as: ((28-day Baseline - 28-day post-Baseline seizure frequency)/28-day Baseline) x 100. A positive value indicates a reduction.

Outcome measures

Measure	Brivaracetam (FAS) n=362 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent Change in Partial-onset Seizure (POS) Frequency From Baseline to Month 3	-5.39 percent change Standard Deviation 215.31

SECONDARY outcome

Timeframe: From Baseline (Day 1) to Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Percent change in POS frequency was defined as: ((28-day Baseline - 28-day post-Baseline seizure frequency)/28-day Baseline) x 100. A positive value indicates a reduction.

Outcome measures

Measure	Brivaracetam (FAS) n=308 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent Change in Partial-onset Seizure (POS) Frequency From Baseline to Month 6	-10.64 percent change Standard Deviation 369.03

SECONDARY outcome

Timeframe: From Baseline (Day 1) to Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Percent change in POS frequency was defined as: ((28-day Baseline - 28-day post-Baseline seizure frequency)/28-day Baseline) x 100. A positive value indicates a reduction.

Outcome measures

Measure	Brivaracetam (FAS) n=230 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent Change in Partial-onset Seizure (POS) Frequency From Baseline to Month 12	7.05 percent change Standard Deviation 351.75

SECONDARY outcome

Timeframe: From Baseline (Day 1) to end of Observation Period (up to Month 12/withdrawal)

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment and were classified as study completers or who withdrew early.

Percent change in POS frequency was defined as: ((28-day Baseline - 28-day post-Baseline seizure frequency)/28-day Baseline) x 100. A positive value indicates a reduction.

Outcome measures

Measure	Brivaracetam (FAS) n=339 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent Change in Partial-onset Seizure (POS) Frequency From Baseline to End of Observation Period	-9.54 percent change Standard Deviation 308.89

SECONDARY outcome

Timeframe: Baseline (Day 1) to Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Response was defined as a (greater than or equal to [>=] 50%) reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=362 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at Month 3	170 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=362 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at Month 3	47.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=308 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at Month 6	146 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=308 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at Month 6	47.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=230 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at Month 12	139 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=230 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at Month 12	60.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to end of Observation Period (up to Month 12/withdrawal)

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment and were classified as study completers or who withdrew early.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=339 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at End of Observation Period	175 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to end of Observation Period (up to Month 12/withdrawal)

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment and were classified as study completers or who withdrew early.

Response was defined as a >=50% reduction from Baseline in seizure frequency.

Outcome measures

Measure	Brivaracetam (FAS) n=339 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Responders Based on Percent Reduction (>=50%) in Partial-onset Seizure (POS) Frequency at End of Observation Period	51.6 percentage of participants

SECONDARY outcome

Timeframe: Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date or participants who discontinued BRV or terminated the study prior to the target visit date (Visit 2 [Month 3] = Day 90) were counted as No.

Outcome measures

Measure	Brivaracetam (FAS) n=497 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=no) at Month 3	81 Participants

SECONDARY outcome

Timeframe: Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date or participants who discontinued BRV or terminated the study prior to the target visit date (Visit 2 [Month 3] = Day 90) were counted as No.

Outcome measures

Measure	Brivaracetam (FAS) n=497 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=no) at Month 3	16.3 percentage of participants

SECONDARY outcome

Timeframe: Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date were counted as a No. Participants who discontinued BRV or terminated the study prior to the target visit date without any seizures recorded up to discontinuation or termination were excluded from the analysis.

Outcome measures

Measure	Brivaracetam (FAS) n=454 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=Missing) at Month 3	81 Participants

SECONDARY outcome

Timeframe: Month 3

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date were counted as a No. Participants who discontinued BRV or terminated the study prior to the target visit date without any seizures recorded up to discontinuation or termination were excluded from the analysis.

Outcome measures

Measure	Brivaracetam (FAS) n=454 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=Missing) at Month 3	17.8 percentage of participants

SECONDARY outcome

Timeframe: Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date or participants who discontinued BRV or terminated the study prior to the target visit date (Visit 3 [Month 6] = Day 180) were counted as No.

Outcome measures

Measure	Brivaracetam (FAS) n=510 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=no) at Month 6	54 Participants

SECONDARY outcome

Timeframe: Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date or participants who discontinued BRV or terminated the study prior to the target visit date (Visit 3 [Month 6] = Day 180) were counted as No.

Outcome measures

Measure	Brivaracetam (FAS) n=510 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=no) at Month 6	10.6 percentage of participants

SECONDARY outcome

Timeframe: Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date were counted as a No. Participants who discontinued BRV or terminated the study prior to the target visit date without any seizures recorded up to discontinuation or termination were excluded from the analysis.

Outcome measures

Measure	Brivaracetam (FAS) n=456 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=Missing) at Month 6	54 Participants

SECONDARY outcome

Timeframe: Month 6

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date were counted as a No. Participants who discontinued BRV or terminated the study prior to the target visit date without any seizures recorded up to discontinuation or termination were excluded from the analysis.

Outcome measures

Measure	Brivaracetam (FAS) n=456 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=Missing) at Month 6	11.8 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date or participants who discontinued BRV or terminated the study prior to the target visit date (Visit 4 [Month 12] = Day 330) were counted as No.

Outcome measures

Measure	Brivaracetam (FAS) n=269 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=no) at Month 12	37 Participants

SECONDARY outcome

Timeframe: Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date or participants who discontinued BRV or terminated the study prior to the target visit date (Visit 4 [Month 12] = Day 330) were counted as No.

Outcome measures

Measure	Brivaracetam (FAS) n=269 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=no) at Month 12	13.8 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date were counted as a No. Participants who discontinued BRV or terminated the study prior to the target visit date without any seizures recorded up to discontinuation or termination were excluded from the analysis.

Outcome measures

Measure	Brivaracetam (FAS) n=269 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Number of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=Missing) at Month 12	37 Participants

SECONDARY outcome

Timeframe: Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS. Here number of participants were included who were evaluable for the assessment.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. Participants with seizures before the visit date were counted as a No. Participants who discontinued BRV or terminated the study prior to the target visit date without any seizures recorded up to discontinuation or termination were excluded from the analysis.

Outcome measures

Measure	Brivaracetam (FAS) n=269 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Percent of Seizure Free Participants (When Discontinuations Were Counted as Seizure Freedom=Missing) at Month 12	13.8 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS.

Time to first seizure was calculated as: Date of first seizure - date of first BRV administration + 1.

Outcome measures

Measure	Brivaracetam (FAS) n=541 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).
Time to First Seizure After First Dose of Brivaracetam	15 days Interval 11.0 to 20.0

SECONDARY outcome

Timeframe: End of Observation Period (up to Month 12/withdrawal)

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. End of Observation Period (up to Month 12), includes participants who are completers or withdrew early.

Outcome measures

Measure

Brivaracetam (FAS) n=541 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).

Number of Seizure Free Participants at End of Observation Period

NA Participants There was no opportunity for the participant to withdraw from the study at the 12-month time point, as they were classified as completers at that stage. Therefore, by definition End of Observation Period (up to Month 12, which includes participants as withdrawn or completers) was identical to Month 12 (including completers alone) results. Hence, the analysis were not performed for this outcome measure.

SECONDARY outcome

Timeframe: End of Observation Period (up to Month 12/withdrawal)

Population: FAS was defined as all participants in the Safety Set (SS) who did not receive BRV before entering this NIS.

Seizure freedom (Yes) was defined as having no seizures recorded in the study on or before the visit date, having not discontinued prior to the visit and having available seizure data at the visit. End of Observation Period (up to Month 12), includes participants who are completers or withdrew early.

Outcome measures

Measure

Brivaracetam (FAS) n=541 Participants Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Full Analysis Set (FAS).

Percent of Seizure Free Participants at End of Observation Period

NA percentage of participants There was no opportunity for the participant to withdraw from the study at the 12-month time point, as they were classified as completers at that stage. Therefore, by definition End of Observation Period (up to Month 12, which includes participants as withdrawn or completers) was identical to Month 12 (including completers alone) results. Hence, the analysis were not performed for this outcome measure.

Adverse Events

Brivaracetam (SS)

Serious events: 80 serious events

Other events: 62 other events

Deaths: 2 deaths

Serious adverse events

Measure	Brivaracetam (SS) n=544 participants at risk Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Safety Set (SS).
Blood and lymphatic system disorders Thrombocytopenia	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Congenital, familial and genetic disorders Cleft lip	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Congenital, familial and genetic disorders Cleft palate	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Eye disorders Diplopia	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Gastrointestinal disorders Abdominal pain lower	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Gastrointestinal disorders Dyspepsia	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Gastrointestinal disorders Oesophageal rupture	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Gastrointestinal disorders Small intestinal obstruction	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
General disorders Death	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
General disorders Malaise	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
General disorders Drug intolerance	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
General disorders Fatigue	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
General disorders Pyrexia	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Infections and infestations Pneumonia	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Infections and infestations Urinary tract infection	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Infections and infestations Actinomycosis	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Infections and infestations Empyema	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Infections and infestations Escherichia urinary tract infection	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Infections and infestations Streptococcal sepsis	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Fall	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Ankle fracture	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Burns third degree	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Foot fracture	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Fracture	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Head injury	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Humerus fracture	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Road traffic accident	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Skin laceration	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Soft tissue injury	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Injury, poisoning and procedural complications Tibia fracture	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Investigations Clinical global impression scale	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Investigations Electroencephalogram	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Musculoskeletal and connective tissue disorders Arthralgia	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Musculoskeletal and connective tissue disorders Neck pain	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Seizure	5.5% 30/544 • Number of events 31 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Generalised tonic-clonic seizure	1.5% 8/544 • Number of events 8 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Partial seizures	0.74% 4/544 • Number of events 4 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Epilepsy	0.55% 3/544 • Number of events 3 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Seizure cluster	0.55% 3/544 • Number of events 3 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Focal dyscognitive seizures	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Petit mal epilepsy	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Status epilepticus	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Change in seizure presentation	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Cognitive disorder	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Dementia Alzheimer's type	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Headache	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Hepatic encephalopathy	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Postictal state	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Nervous system disorders Tonic convulsion	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Pregnancy, puerperium and perinatal conditions Gestational diabetes	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Suicidal ideation	1.7% 9/544 • Number of events 9 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Aggression	1.1% 6/544 • Number of events 6 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Affective disorder	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Agitation	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Mood altered	0.37% 2/544 • Number of events 2 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Anger	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Anxiety	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Behaviour disorder	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Depressed mood	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Drug abuse	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Mood swings	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Paranoia	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Psychiatric disorders Personality change	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Renal and urinary disorders Nephrolithiasis	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Skin and subcutaneous tissue disorders Rash	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Surgical and medical procedures Abortion induced	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.
Surgical and medical procedures Epilepsy surgery	0.18% 1/544 • Number of events 1 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.

Other adverse events

Measure	Brivaracetam (SS) n=544 participants at risk Participants were treated with commercially available BRV as prescribed by treating physicians, in accordance with current clinical practice and in accordance with the approved European Summary of Product Characteristics (SmPC). Participants formed the Safety Set (SS).
General disorders Drug ineffective	11.4% 62/544 • Number of events 63 • From Baseline up to Month 12 Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) occurring on or after the date of first BRV administration.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60