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Clinical Trial Results:
An Open-Label, Multicenter, Follow-up Study to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

Summary
EudraCT number	2019-001205-25
Trial protocol	Outside EU/EEA
Global end of trial date	24 Dec 2024

Results information
Results version number	v1(current)
This version publication date	27 Jun 2025
First version publication date	27 Jun 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

EP0085

ISRCTN number

US NCT number

NCT03250377

WHO universal trial number (UTN)

Sponsor organisation name

UCB Biopharma SRL

Sponsor organisation address

Allée de la Recherche 60, Brussels, Belgium, 1070

Public contact

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

Scientific contact

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

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

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

06 Feb 2025

Is this the analysis of the primary completion data?

Yes

Primary completion date

24 Dec 2024

Global end of trial reached?

Yes

Global end of trial date

24 Dec 2024

Was the trial ended prematurely?

Main objective of the trial

Evaluate the long-term safety and tolerability of BRV in focal epilepsy subjects with partial seizures

Protection of trial subjects

Invasive treatment is not planned in Protocol

Background therapy

Background therapy as permitted in the protocol

Evidence for comparator

Not Applicable

Actual start date of recruitment

05 Aug 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 132

Country: Number of subjects enrolled

China: 75

Worldwide total number of subjects

207

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

192

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study started to enroll participants in August 2017 and concluded in December 2024.

Screening details

The Participant Flow refers to the Safety Set (SS). Study consisted of the Evaluation period (duration for rollover participants - 84 Months and for direct enrollers - 39 Months); Down-titration period (4 weeks); drug-free period (2 weeks).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

EP0083 Placebo

Arm description

Participants who received Placebo in study EP0083 (NCT03083665) and completed the Treatment and Transition Period of study EP0083 are rolled over to this study and received brivaracetam (BRV) 50 milligram per day (mg/day) two times (bid) (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. up to 84 months). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants’ s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

BRV

Other name

Briviact

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brivaracetam at prespecified time-points.

EP0083 BRV All

Arm description

Participants rolled over from study EP0083 received BRV 50 mg/day bid (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. up to 84 months). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants’ s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

BRV

Other name

Briviact

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brivaracetam at prespecified time-points.

N01379 BRV

Arm description

Participants rolled over from study N01379 (NCT01339559) (core study N01358 [NCT01261325]) received BRV 200 mg/day during the evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. up to 84 months). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants’ s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

BRV

Other name

Briviact

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brivaracetam at prespecified time-points.

Direct Enrollers BRV

Arm description

Participants directly enrolled in this study received BRV 50 mg bid (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. Up to 84 Month, however, were evaluated for 39 months only due to late enrollment). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants’ s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study.

Arm type

Experimental

Investigational medicinal product name

Brivaracetam

Investigational medicinal product code

BRV

Other name

Briviact

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brivaracetam at prespecified time-points.

Number of subjects in period 1	EP0083 Placebo	EP0083 BRV All	N01379 BRV	Direct Enrollers BRV
Started	54	112	7	34
Evaluation Period	54	112	7	34
Down-Titration Period	20 ^[1]	32 ^[2]	5	15 ^[3]
Study Drug-Free Period	39	76	5	17 ^[4]
Completed	37	74	4	20
Not completed	17	38	3	14
Epilepsy Surgery	-	1	2	-
Subjects underweight; intolerant to study drugs	-	1	-	-
Subjects felt no effect;want to discontinue study	-	1	-	-
Subject did not follow procedure or study drug	-	1	-	-
Subjects did not follow procedures or medication	-	1	-	-
Investigator's Judgment	1	-	-	-
Pregnancy Event	-	1	-	-
Subject moved to kanagawa (faraway from clinic)	-	1	-	-
PI’s opinion:Subject noncompliant with medication	-	1	-	-
Patient requested to change hospital	-	-	-	1
Admission To Geriatric Health Facility	-	-	-	1
Consent withdrawn by subject	7	7	-	4
Request From The Sponsor	-	1	-	-
Adverse event, non-fatal	2	4	-	4
She wanted to change other therapeutic medication	1	-	-	-
The Subject Go Abroad and Not Return	1	-	-	-
Subject stopped drug; did not wish to continue	-	1	-	-
Lost to follow-up	-	1	-	-
Lack of efficacy	5	14	1	3
Protocol deviation	-	2	-	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who had an Early Discontinuation Visit (EDV) and had at least 1 dose of study drug after the date of EDV were considered to start Down-Titration Period.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who had an Early Discontinuation Visit (EDV) and had at least 1 dose of study drug after the date of EDV were considered to start Down-Titration Period.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who had at least one contact after the date of the last dose of BRV were considered to start study Drug-Free period.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who had an Early Discontinuation Visit (EDV) and had at least 1 dose of study drug after the date of EDV were considered to start Down-Titration Period.

Baseline characteristics

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Reporting group title

EP0083 Placebo

Reporting group description

Reporting group title

EP0083 BRV All

Reporting group description

Reporting group title

N01379 BRV

Reporting group description

Reporting group title

Direct Enrollers BRV

Reporting group description

Reporting group values	EP0083 Placebo	EP0083 BRV All	N01379 BRV	Direct Enrollers BRV	Total
Number of subjects	54	112	7	34	207
Age Categorical
Units: participants
12 - <18 yrs	2	4	0	1	7
18 - <65 yrs	52	104	7	29	192
65 - <85 yrs	0	4	0	3	7
>=85 yrs	0	0	0	1	1
Age Continuous
Units: years
arithmetic mean (standard deviation)	34.5 ( 11.6 )	35.8 ( 13.5 )	40.7 ( 10.9 )	42.2 ( 18.6 )	-
Sex: Female, Male
Units: participants
Female	32	53	3	19	107
Male	22	59	4	15	100

End points

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Reporting group title

EP0083 Placebo

Reporting group description

Reporting group title

EP0083 BRV All

Reporting group description

Reporting group title

N01379 BRV

Reporting group description

Reporting group title

Direct Enrollers BRV

Reporting group description

Primary: Percentage of participants with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Percentage of participants with Treatment-Emergent Adverse Events (TEAEs) ^[1]

End point description

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs (TEAEs) were defined as AEs that had onset on or after the day of first BRV dose in EP0085 study. The Safety Set consisted of all participants who took at least 1 dose of study medication.

End point type

Primary

End point timeframe

From Baseline until end of the safety follow up (up to 88.5 months)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	EP0083 Placebo	EP0083 BRV All	N01379 BRV	Direct Enrollers BRV
Number of subjects analysed	54	112	7	34
Units: percentage of participants
number (not applicable)	88.9	95.5	100	94.1

No statistical analyses for this end point

Secondary: 50 percent (%) Responder rate in partial seizure frequency per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

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End point title

50 percent (%) Responder rate in partial seizure frequency per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants ^[2]

End point description

The seizure frequency was calculated as number of seizures per 28 days. 50% responders were defined as a participant with a >= 50% reduction in seizure frequency from the baseline period over the post-baseline period. Percentages are based on the number of participants who performed the seizure assessment at each time point. The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.

End point type

Secondary

End point timeframe

Baseline of EP0083 or N01358 and by every 3-month periods over the Evaluation Period (up to 84 months)

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 50 % Responder rate in partial seizure frequency per 28 days for arm Direct Enrollers is reported in a separate endpoint. Therefore, no data was reported for this arm in this endpoint

End point values	EP0083 Placebo	EP0083 BRV All	N01379 BRV
Number of subjects analysed	54	112	7
Units: percentage of responders
number (not applicable)	66.7	47.3	57.1

No statistical analyses for this end point

Secondary: Percent change in partial seizure frequency (PSF) per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

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End point title

Percent change in partial seizure frequency (PSF) per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants ^[3]

End point description

The seizure frequency was calculated as number of seizures per 28 days. Percent change of 28 day PSF from Baseline was defined as the percentage reduction of 28 day PSF for a designated post-baseline period in EP0085 compared with the Baseline 28 day PSF in the core study. Change in seizure frequency from Baseline was calculated: percent change = ([Baseline 28 day PSF − Post Baseline 28 day PSF]/[Baseline 28 day PSF]) × 100. For rollovers, the Baseline period was obtained from the core studies of EP0083 and N01358 directly. A negative value in percent change from Baseline indicates a decrease in PSF from Baseline. The Full Analysis Set (FAS) consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on Daily Record Card (DRC) during the Evaluation Period.

End point type

Secondary

End point timeframe

Baseline of EP0083 or N01358 and by every 3-month periods over the Evaluation Period (up to 84 months)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Percent change in partial seizure frequency (PSF) per 28 days for arm Direct Enrollers is reported in a separate endpoint. Therefore, no data was reported for this arm in this endpoint.

End point values	EP0083 Placebo	EP0083 BRV All	N01379 BRV
Number of subjects analysed	54	112	7
Units: percent change
median (full range (min-max))	60.6 (-87 to 100)	43.2 (-497 to 100)	67.0 (-72 to 100)

No statistical analyses for this end point

Secondary: 50 % responder rate in partial seizure frequency per 28 days over the Evaluation Period for directly enrolled study participants

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End point title

50 % responder rate in partial seizure frequency per 28 days over the Evaluation Period for directly enrolled study participants ^[4]

End point description

The seizure frequency for directly enrolled participants was calculated as number of seizures per 28 days from 8 weeks prior to BRV administration. 50% responders were defined as a participant with a >= 50% reduction in seizure frequency from the Baseline Period over the post-baseline period. Percentages are based on the number of participants who performed the seizure assessment at each time point. For direct enrollers, the Baseline Period was defined as seizure counts collected from 8 weeks prior to the first BRV administration in EP0085. The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.

End point type

Secondary

End point timeframe

Baseline (8 weeks prior to BRV administration), every 3 months throughout the evaluation period (up to 39 months)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 50 % Responder rate in partial seizure frequency per 28 days for the arms of rollover study participants is reported in a separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Direct Enrollers BRV
Number of subjects analysed	34
Units: percentage of responders
number (not applicable)	26.5

No statistical analyses for this end point

Secondary: Percent change in partial seizure frequency per 28 days from Baseline of directly enrolled study participants to the Evaluation Period

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End point title

Percent change in partial seizure frequency per 28 days from Baseline of directly enrolled study participants to the Evaluation Period ^[5]

End point description

The seizure frequency was calculated as number of seizures per 28 days. For direct enrollers, the Baseline Period was defined as seizure counts collected from 8 weeks prior to the first BRV administration in EP0085. Change in seizure frequency is calculated as the seizure frequency at the evaluation time point minus the seizure frequency at Baseline of directly enrolled participants. A negative value in percent change from Baseline indicates a decrease in PSF from Baseline. The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.

End point type

Secondary

End point timeframe

Baseline (8 weeks prior to BRV administration), every 3 months throughout the evaluation period (up to 39 months)

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Percent change in partial seizure frequency per 28 days for the arms of rollover study participants is reported in a separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Direct Enrollers BRV
Number of subjects analysed	34
Units: percent change
median (full range (min-max))	-32.6 (-3691 to 100)

No statistical analyses for this end point

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for rollover study participants

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End point title

Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for rollover study participants ^[6]

End point description

A study participant was considered seizure free, if no seizure occurred during 6 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

During the Evaluation Period (up to 84 months)

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The percentage of participants continuously seizure-free for partial seizure and all seizure types for at least 6 months for arm Direct Enrollers is reported in a separate endpoint. Therefore, no data was reported for this arm in this endpoint.

End point values	EP0083 Placebo	EP0083 BRV All	N01379 BRV
Number of subjects analysed	52	101	7
Units: percentage of participants
number (not applicable)	15.4	19.8	28.6

No statistical analyses for this end point

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for rollover study participants

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End point title

Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for rollover study participants ^[7]

End point description

A study participant was considered seizure free, if no seizure occurred during 12 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

During the Evaluation Period (up to 84 months)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The percentage of participants continuously seizure-free for partial seizure and all seizure types for at least 12 months for the arm Direct Enrollers is reported in a separate endpoint. Therefore, no data was reported for this arm in this endpoint.

End point values	EP0083 Placebo	EP0083 BRV All	N01379 BRV
Number of subjects analysed	48	93	6
Units: percentage of participants
number (not applicable)	8.3	14.0	33.3

No statistical analyses for this end point

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for rollover study participants

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End point title

Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for rollover study participants ^[8]

End point description

A study participant was considered seizure free (partial, all epileptic seizure), if no seizure occurred during the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.

End point type

Secondary

End point timeframe

During the Evaluation Period (up to 84 months)

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period is reported under a separate endpoint for the Direct Enrollers arm. Therefore, no data was reported for this arm in this endpoint.

End point values	EP0083 Placebo	EP0083 BRV All	N01379 BRV
Number of subjects analysed	54	112	7
Units: percentage of participants
number (not applicable)
Participants with partial seizure-freedom	1.9	7.1	14.3
Participants with all-type seizure-freedom	1.9	7.1	14.3

No statistical analyses for this end point

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for directly enrolled study participants

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End point title

Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for directly enrolled study participants ^[9]

End point description

End point type

Secondary

End point timeframe

During the Evaluation Period (up to 39 months)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for arms of rollover study participants is reported in a separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Direct Enrollers BRV
Number of subjects analysed	34
Units: percentage of participants
number (not applicable)
Participants with partial seizure-freedom	5.9
Participants with all-type seizure-freedom	5.9

No statistical analyses for this end point

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for directly enrolled study participants

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End point title

End point description

End point type

Secondary

End point timeframe

During the Evaluation Period (up to 39 months)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The percentage of participants continuously seizure-free for partial seizure and all seizure types for at least 6 months for arms of rollover study participants is reported in a separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Direct Enrollers BRV
Number of subjects analysed	29
Units: percentage of participants
number (not applicable)	24.1

No statistical analyses for this end point

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for directly enrolled study participants

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End point title

End point description

End point type

Secondary

End point timeframe

During the Evaluation Period (up to 39 months)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The percentage of participants continuously seizure-free for partial seizure and all seizure types for at least 12 months for the arms of rollover study participants is reported in a separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Direct Enrollers BRV
Number of subjects analysed	26
Units: percentage of participants
number (not applicable)	15.4

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline until end of the safety follow up (up to 88.5 months)

Adverse event reporting additional description

Treatment-emergent AEs (TEAEs) were defined as AEs that had onset on or after the day of first BRV dose in EP0085 study. The Safety Set consisted of all participants who took at least 1 dose of study medication.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

EP0083 Placebo

Reporting group description

Reporting group title

Direct Enrollers BRV

Reporting group description

Participants directly enrolled in this study received BRV 50mg bid (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. Up to 84 Month, however, were evaluated for 39 months only due to late enrollment). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants’ s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study.

Reporting group title

N01379 BRV

Reporting group description

Reporting group title

EP0083 BRV All

Reporting group description

Serious adverse events	EP0083 Placebo	Direct Enrollers BRV	N01379 BRV	EP0083 BRV All
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 54 (11.11%)	6 / 34 (17.65%)	5 / 7 (71.43%)	23 / 112 (20.54%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian clear cell carcinoma
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Brain operation
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	2 / 7 (28.57%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abortion induced
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cranioplasty
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	1 / 7 (14.29%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vagal nerve stimulator implantation
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Endometriosis
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst ruptured
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian haemorrhage
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
subjects affected / exposed	0 / 54 (0.00%)	2 / 34 (5.88%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	2 / 112 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mental disorder due to a general medical condition
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Self injurious behaviour
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain contusion
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Scapula fracture
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	1 / 7 (14.29%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ataxia
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Parkinsonism
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure cluster
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 54 (1.85%)	1 / 34 (2.94%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Eyelid ptosis
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Gallbladder polyp
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Synovial cyst
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	1 / 7 (14.29%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone cyst
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pericoronitis
subjects affected / exposed	1 / 54 (1.85%)	0 / 34 (0.00%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Corona virus infection
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pilonidal cyst
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 54 (0.00%)	1 / 34 (2.94%)	0 / 7 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis bacterial
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 54 (0.00%)	0 / 34 (0.00%)	0 / 7 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	EP0083 Placebo	Direct Enrollers BRV	N01379 BRV	EP0083 BRV All
Total subjects affected by non serious adverse events
subjects affected / exposed	41 / 54 (75.93%)	27 / 34 (79.41%)	6 / 7 (85.71%)	87 / 112 (77.68%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	7 / 54 (12.96%)	4 / 34 (11.76%)	2 / 7 (28.57%)	11 / 112 (9.82%)
occurrences all number	8	8	10	19
Nervous system disorders
Dizziness
subjects affected / exposed	12 / 54 (22.22%)	5 / 34 (14.71%)	3 / 7 (42.86%)	17 / 112 (15.18%)
occurrences all number	13	5	4	21
Headache
subjects affected / exposed	10 / 54 (18.52%)	3 / 34 (8.82%)	0 / 7 (0.00%)	21 / 112 (18.75%)
occurrences all number	17	8	0	30
Somnolence
subjects affected / exposed	14 / 54 (25.93%)	6 / 34 (17.65%)	2 / 7 (28.57%)	8 / 112 (7.14%)
occurrences all number	17	8	2	13
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	9 / 54 (16.67%)	6 / 34 (17.65%)	1 / 7 (14.29%)	21 / 112 (18.75%)
occurrences all number	14	7	2	43
Gastrointestinal disorders
Nausea
subjects affected / exposed	5 / 54 (9.26%)	1 / 34 (2.94%)	0 / 7 (0.00%)	11 / 112 (9.82%)
occurrences all number	7	2	0	13
Diarrhoea
subjects affected / exposed	3 / 54 (5.56%)	4 / 34 (11.76%)	0 / 7 (0.00%)	14 / 112 (12.50%)
occurrences all number	4	4	0	20
Abdominal pain
subjects affected / exposed	3 / 54 (5.56%)	2 / 34 (5.88%)	1 / 7 (14.29%)	6 / 112 (5.36%)
occurrences all number	5	3	2	8
Vomiting
subjects affected / exposed	3 / 54 (5.56%)	3 / 34 (8.82%)	0 / 7 (0.00%)	6 / 112 (5.36%)
occurrences all number	6	6	0	6
Stomatitis
subjects affected / exposed	4 / 54 (7.41%)	3 / 34 (8.82%)	0 / 7 (0.00%)	4 / 112 (3.57%)
occurrences all number	11	5	0	4
Constipation
subjects affected / exposed	5 / 54 (9.26%)	1 / 34 (2.94%)	0 / 7 (0.00%)	5 / 112 (4.46%)
occurrences all number	6	1	0	5
Abdominal pain upper
subjects affected / exposed	2 / 54 (3.70%)	2 / 34 (5.88%)	2 / 7 (28.57%)	6 / 112 (5.36%)
occurrences all number	3	2	2	9
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	5 / 54 (9.26%)	2 / 34 (5.88%)	0 / 7 (0.00%)	13 / 112 (11.61%)
occurrences all number	6	2	0	17
Oropharyngeal pain
subjects affected / exposed	5 / 54 (9.26%)	5 / 34 (14.71%)	1 / 7 (14.29%)	11 / 112 (9.82%)
occurrences all number	12	5	1	19
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	4 / 54 (7.41%)	1 / 34 (2.94%)	0 / 7 (0.00%)	7 / 112 (6.25%)
occurrences all number	10	1	0	11
Psychiatric disorders
Insomnia
subjects affected / exposed	5 / 54 (9.26%)	2 / 34 (5.88%)	1 / 7 (14.29%)	7 / 112 (6.25%)
occurrences all number	6	2	1	7
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	3 / 54 (5.56%)	2 / 34 (5.88%)	0 / 7 (0.00%)	7 / 112 (6.25%)
occurrences all number	3	2	0	9
Pain in extremity
subjects affected / exposed	2 / 54 (3.70%)	2 / 34 (5.88%)	0 / 7 (0.00%)	8 / 112 (7.14%)
occurrences all number	2	2	0	12
Infections and infestations
Corona virus infection
subjects affected / exposed	13 / 54 (24.07%)	11 / 34 (32.35%)	0 / 7 (0.00%)	32 / 112 (28.57%)
occurrences all number	13	11	0	34
Nasopharyngitis
subjects affected / exposed	20 / 54 (37.04%)	9 / 34 (26.47%)	3 / 7 (42.86%)	18 / 112 (16.07%)
occurrences all number	88	19	6	68
Upper respiratory tract infection
subjects affected / exposed	5 / 54 (9.26%)	1 / 34 (2.94%)	0 / 7 (0.00%)	23 / 112 (20.54%)
occurrences all number	11	1	0	36
Cystitis
subjects affected / exposed	3 / 54 (5.56%)	3 / 34 (8.82%)	0 / 7 (0.00%)	5 / 112 (4.46%)
occurrences all number	3	13	0	7

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Were there any global substantial amendments to the protocol? Yes

28 Jan 2019

Protocol amendment 2 (dated 28 Jan 2019): A total of 32 participants were enrolled at the time of this amendment. The following changes were made: • Updated the number of participants based on randomization of EP0083 and N01379 sites in Japan. • Updated safety variables. • Updated participating countries. • Included IEC. In addition, minor administrative edits, including typographical changes for formatting, were made.

20 Nov 2019

Protocol amendment 3 (dated 20 Nov 2019): A total of 56 participants were enrolled at the time of this amendment. The following changes were made: • Updated the Sponsor/Local Legal Representatives. • Added China as a participating country. • Included serious adverse event (SAE) reporting information for China. • Updated the number of participants expected to enter the study. • Changed exploratory safety variable to other safety variable. In addition, minor administrative edits, including typographical changes for formatting, were made.

15 Mar 2023

Protocol amendment 4 (dated 15 Mar 2023): A total of 207 participants were enrolled at the time of this amendment. The following changes were made: • Updated the Study Contact Information. • Changed the primary safety variable from adverse events (AEs) to treatment-emergent adverse events (TEAEs), in alignment with other studies across the brivaracetam development program. • Deleted mental status/psychiatric status from the list of other safety variables to be collected; abnormal findings upon physical or neurological examination were to be recorded as AEs. • Changed the planned duration of EP0085 to allow participants to continue in the study until market approval in countries where market approval will be requested and for 2 years in countries where market approval will not be requested or obtained. • Added details regarding EP0085 study participants’ participation in EP0118 for clarification purposes. • Added to the study withdrawal criteria that a suicide attempt will necessitate a participant’s withdrawal from the study. - This will eliminate the risk of another suicide attempt or completed suicide during the study in cases where the participant’s recent suicidal ideation was not accurately reflected by the Columbia Suicide Severity Rating Scale (C SSRS). • Added information regarding numbering of directly enrolled participants entering the study. • Added a statement for TEAE and SAE disclosure on public registries per the current UCB protocol template. • Removed 2 efficacy analyses from the previous list of analyses planned for all participants per SAP amendments implemented following EP0085 protocol approval. • Corrected the handling of protocol deviations text as there was no pooling of stratification levels for statistical analysis and there were no statistical assumptions for the primary analysis for this study. In addition, minor clarifications and administrative edits including typographical changes for formatting were made.

Were there any global interruptions to the trial? No

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

None reported

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Clinical Trial Results:
An Open-Label, Multicenter, Follow-up Study to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with Treatment-Emergent Adverse Events (TEAEs)

Primary: Percentage of participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary: 50 percent (%) Responder rate in partial seizure frequency per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: 50 percent (%) Responder rate in partial seizure frequency per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: Percent change in partial seizure frequency (PSF) per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: Percent change in partial seizure frequency (PSF) per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: 50 % responder rate in partial seizure frequency per 28 days over the Evaluation Period for directly enrolled study participants

Secondary: 50 % responder rate in partial seizure frequency per 28 days over the Evaluation Period for directly enrolled study participants

Secondary: Percent change in partial seizure frequency per 28 days from Baseline of directly enrolled study participants to the Evaluation Period

Secondary: Percent change in partial seizure frequency per 28 days from Baseline of directly enrolled study participants to the Evaluation Period

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for directly enrolled study participants

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results: An Open-Label, Multicenter, Follow-up Study to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with Treatment-Emergent Adverse Events (TEAEs)

Primary: Percentage of participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary: 50 percent (%) Responder rate in partial seizure frequency per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: 50 percent (%) Responder rate in partial seizure frequency per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: Percent change in partial seizure frequency (PSF) per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: Percent change in partial seizure frequency (PSF) per 28 days from Baseline of EP0083 or N01358 to the Evaluation Period for rollover study participants

Secondary: 50 % responder rate in partial seizure frequency per 28 days over the Evaluation Period for directly enrolled study participants

Secondary: 50 % responder rate in partial seizure frequency per 28 days over the Evaluation Period for directly enrolled study participants

Secondary: Percent change in partial seizure frequency per 28 days from Baseline of directly enrolled study participants to the Evaluation Period

Secondary: Percent change in partial seizure frequency per 28 days from Baseline of directly enrolled study participants to the Evaluation Period

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for rollover study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 6 months during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for directly enrolled study participants

Secondary: Percentage of participants continuously seizure-free for partial seizure and all seizure types (partial, generalized, and unclassified epileptic seizure) for at least 12 months during the Evaluation Period for directly enrolled study participants

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An Open-Label, Multicenter, Follow-up Study to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization