Trial Outcomes & Findings for Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures (NCT NCT01261325)

NCT ID: NCT01261325

Last Updated: 2022-07-22

Results Overview

Primary endpoint: United States of America (FDA)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

768 participants

Primary outcome timeframe

12 week Treatment Period

Results posted on

2022-07-22

Participant Flow

Recruitment for the N01358 study began in December 2010. The study concluded in May 2014.

The Participant Flow and Baseline Demographics data is taken from the Randomized Set (RS). The RS consists of all subjects who were randomized.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo tablets administered twice daily	Brivaracetam 100 mg/Day Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day Brivaracetam 100 mg administered twice daily
Overall Study STARTED	263	254	251
Overall Study COMPLETED	246	225	225
Overall Study NOT COMPLETED	17	29	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo tablets administered twice daily	Brivaracetam 100 mg/Day Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day Brivaracetam 100 mg administered twice daily
Overall Study Lack of Efficacy	1	1	0
Overall Study Withdrawal by Subject	2	2	4
Overall Study SAE, non-fatal	1	5	1
Overall Study AE, non-serious non-fatal	9	15	13
Overall Study SAE, non-fatal+AE, non-serious non-fatal	0	1	1
Overall Study Non Compliance	2	0	0
Overall Study Patient Randomized by Mistake	0	1	0
Overall Study Erroneously Randomized	1	0	0
Overall Study Screen Failure	1	0	0
Overall Study Randomized in Error	0	0	1
Overall Study Protocol Violation	0	3	1
Overall Study Lost to Follow-up	0	1	3
Overall Study AE, serious fatal	0	0	2

Baseline Characteristics

Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=263 Participants Matching placebo tablets administered twice daily	Brivaracetam 100 mg/Day n=254 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=251 Participants Brivaracetam 100 mg administered twice daily	Total Title n=768 Participants
Age, Continuous	39.8 years STANDARD_DEVIATION 12.8 • n=39 Participants	39.0 years STANDARD_DEVIATION 13.4 • n=41 Participants	39.7 years STANDARD_DEVIATION 12.8 • n=35 Participants	39.5 years STANDARD_DEVIATION 13.0 • n=31 Participants
Sex: Female, Male Female	128 Participants n=39 Participants	152 Participants n=41 Participants	117 Participants n=35 Participants	397 Participants n=31 Participants
Sex: Female, Male Male	135 Participants n=39 Participants	102 Participants n=41 Participants	134 Participants n=35 Participants	371 Participants n=31 Participants
Weight	76.1 kilograms STANDARD_DEVIATION 19.9 • n=39 Participants	74.1 kilograms STANDARD_DEVIATION 16.8 • n=41 Participants	75.5 kilograms STANDARD_DEVIATION 19.0 • n=35 Participants	75.2 kilograms STANDARD_DEVIATION 18.6 • n=31 Participants
Height	168.4 centimeters STANDARD_DEVIATION 10.0 • n=39 Participants	166.6 centimeters STANDARD_DEVIATION 9.8 • n=41 Participants	168.7 centimeters STANDARD_DEVIATION 9.9 • n=35 Participants	167.9 centimeters STANDARD_DEVIATION 9.9 • n=31 Participants
BMI	26.6 kg/m^2 STANDARD_DEVIATION 5.7 • n=39 Participants	26.7 kg/m^2 STANDARD_DEVIATION 5.6 • n=41 Participants	26.4 kg/m^2 STANDARD_DEVIATION 6.0 • n=35 Participants	26.6 kg/m^2 STANDARD_DEVIATION 5.8 • n=31 Participants
Racial Group American Indian or Alaska Native	10 participants n=39 Participants	8 participants n=41 Participants	11 participants n=35 Participants	29 participants n=31 Participants
Racial Group Asian	32 participants n=39 Participants	32 participants n=41 Participants	29 participants n=35 Participants	93 participants n=31 Participants
Racial Group Black or African American	11 participants n=39 Participants	8 participants n=41 Participants	7 participants n=35 Participants	26 participants n=31 Participants
Racial Group White	190 participants n=39 Participants	183 participants n=41 Participants	183 participants n=35 Participants	556 participants n=31 Participants
Racial Group Other	17 participants n=39 Participants	21 participants n=41 Participants	18 participants n=35 Participants	56 participants n=31 Participants
Racial Group Missing	3 participants n=39 Participants	2 participants n=41 Participants	3 participants n=35 Participants	8 participants n=31 Participants

PRIMARY outcome

Timeframe: 12 week Treatment Period

Population: Analysis population consists of the Intent-to-Treat (ITT) Population, which is all randomized subjects who received at least 1 dose of study medication and have at least 1 post-Baseline seizure diary.

Primary endpoint: United States of America (FDA)

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=252 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=249 Participants Brivaracetam 100 mg administered twice daily	Placebo n=259 Participants Matching placebo tablets administered twice daily
Percent Reduction Over Placebo for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration	22.8 Percentage of reduction	23.2 Percentage of reduction	0 Percentage of reduction

PRIMARY outcome

Timeframe: Baseline to 12 week Treatment Period

Primary Endpoint: European Regulatory Authorities A responder is a participant who experienced a 50% or greater reduction in partial onset seizure (Type I) frequency over the Treatment Period standardized to a 28-day duration.

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration Responders	21.6 Percentage of subjects	38.9 Percentage of subjects	37.8 Percentage of subjects
50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration Non-Responders	78.4 Percentage of subjects	61.1 Percentage of subjects	62.2 Percentage of subjects

SECONDARY outcome

Timeframe: Baseline to 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
Percent Change in Partial Onset Seizure (Type I) Frequency From the Baseline to the Treatment Period	17.6 percentage of change Interval -8.3 to 46.0	37.2 percentage of change Interval 0.1 to 69.4	35.6 percentage of change Interval 4.8 to 66.2

SECONDARY outcome

Timeframe: Baseline to 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period <-25 %	16.6 percentage of subjects	14.3 percentage of subjects	10.8 percentage of subjects
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period -25 % to <25 %	40.5 percentage of subjects	28.6 percentage of subjects	29.3 percentage of subjects
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period 25 % to <50 %	21.2 percentage of subjects	18.3 percentage of subjects	22.1 percentage of subjects
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period 50 % to <75 %	13.9 percentage of subjects	19.0 percentage of subjects	18.1 percentage of subjects
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period 75 % to <100 %	6.9 percentage of subjects	13.9 percentage of subjects	13.7 percentage of subjects
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period 100 %	0.8 percentage of subjects	6.0 percentage of subjects	6.0 percentage of subjects

SECONDARY outcome

Timeframe: 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period Seizure free	0.8 percentage of subjects	5.2 percentage of subjects	4.0 percentage of subjects
Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period No seizures but discontinued	0.4 percentage of subjects	1.2 percentage of subjects	1.2 percentage of subjects
Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period Not seizure free	98.8 percentage of subjects	93.7 percentage of subjects	94.8 percentage of subjects

SECONDARY outcome

Timeframe: 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
All Seizure Frequency (Type I + II + III) During the 12-week Treatment Period	8.7 number of seizures/ 28-day Interval 4.3 to 23.6	6.3 number of seizures/ 28-day Interval 2.7 to 17.8	5.8 number of seizures/ 28-day Interval 2.3 to 14.2

SECONDARY outcome

Timeframe: 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
Time to the First Type I Seizure During the Treatment Period	3 days Interval 2.0 to 3.0	5 days Interval 3.0 to 7.0	6 days Interval 4.0 to 7.0

SECONDARY outcome

Timeframe: 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
Time to the Fifth Type I Seizure During the Treatment Period	16 days Interval 12.0 to 19.0	21 days Interval 17.0 to 25.0	23 days Interval 20.0 to 26.0

SECONDARY outcome

Timeframe: 12 week Treatment Period

Outcome measures

Outcome measures
Measure	Brivaracetam 100 mg/Day n=259 Participants Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=252 Participants Brivaracetam 100 mg administered twice daily	Placebo n=249 Participants Matching placebo tablets administered twice daily
Time to the Tenth Type I Seizure During the Treatment Period	32 days Interval 24.0 to 36.0	37 days Interval 29.0 to 46.0	43 days Interval 36.0 to 49.0

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 61 other events

Deaths: 0 deaths

Brivaracetam 100 mg/Day

Serious events: 8 serious events

Other events: 96 other events

Deaths: 0 deaths

Brivaracetam 200 mg/Day

Serious events: 8 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=261 participants at risk Matching placebo tablets administered twice daily	Brivaracetam 100 mg/Day n=253 participants at risk Brivaracetam 50 mg administered twice daily	Brivaracetam 200 mg/Day n=250 participants at risk Brivaracetam 100 mg administered twice daily
General disorders Fatigue	3.8% 10/261 • Number of events 10 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	7.5% 19/253 • Number of events 19 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	11.6% 29/250 • Number of events 32 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.
Infections and infestations Urinary tract infection	3.1% 8/261 • Number of events 8 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	5.1% 13/253 • Number of events 13 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	0.80% 2/250 • Number of events 2 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.
Nervous system disorders Somnolence	7.7% 20/261 • Number of events 20 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	19.4% 49/253 • Number of events 53 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	16.8% 42/250 • Number of events 43 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.
Nervous system disorders Dizziness	5.0% 13/261 • Number of events 14 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	10.3% 26/253 • Number of events 27 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	14.4% 36/250 • Number of events 38 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.
Nervous system disorders Headache	8.4% 22/261 • Number of events 30 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	6.7% 17/253 • Number of events 18 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.	8.0% 20/250 • Number of events 21 • Treatment-emergent Adverse Events (TEAE) were collected during the study up to week 18 TEAEs are comprised of the Safety Population, which consists of all randomized subjects who receive at least 1 dose of study medication. The Non-serious Adverse Events section represents a \>= 5% threshold of subjects experiencing Non-serious TEAEs in any treatment group and not the total population.

Additional Information

Study Director

UCB Clinical Trial Call Center

Phone: +1 887 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee UCB has \> 60 but \<= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that the results shall be published regardless of outcome.
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