Trial Outcomes & Findings for Open-label, Pharmacokinetic, Safety and Efficacy Study of Adjunctive Brivaracetam in Children With Epilepsy. (NCT NCT00422422)

NCT ID: NCT00422422

Last Updated: 2018-07-11

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: Day 21
• Results posted on: 2018-07-11

Participant Flow

The N01263 study began recruitment in July 2011, with subjects enrolled in the European Union, Mexico, and the United States. The study concluded in March 2013.

Participant milestones

Measure	Brivaracetam (ES) Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5
Overall Study STARTED	100
Overall Study COMPLETED	90
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	Brivaracetam (ES) Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5
Overall Study Lack of Efficacy	1
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	2
Overall Study SAE, non-fatal	1
Overall Study AE, non-serious non-fatal	5

Baseline Characteristics

Open-label, Pharmacokinetic, Safety and Efficacy Study of Adjunctive Brivaracetam in Children With Epilepsy.

Baseline characteristics by cohort

Measure	Brivaracetam (ES) n=100 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5
Age, Continuous	6.3 years STANDARD_DEVIATION 4.8 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants
Weight	24.2 kilograms STANDARD_DEVIATION 16.2 • n=5 Participants
Height	111.8 centimeters STANDARD_DEVIATION 32.9 • n=5 Participants
BMI	17.1 kg/m^2 STANDARD_DEVIATION 3.4 • n=5 Participants
Racial Group Black or African American	4 participants n=5 Participants
Racial Group White	80 participants n=5 Participants
Racial Group Other	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 21

Outcome measures

Measure

Brivaracetam (PPS) n=12 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Mean Trough Plasma Concentration at 3rd Level for Age Range ≥1 Month to <2 Years

0.825 ug/mL Standard Deviation 0.826

PRIMARY outcome

Timeframe: Day 21

Outcome measures

Measure

Brivaracetam (PPS) n=22 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Mean Trough Plasma Concentration at 3rd Level for Age Range ≥2 to <12 Years

0.967 ug/mL Standard Deviation 0.536

PRIMARY outcome

Timeframe: Day 21

Outcome measures

Measure

Brivaracetam (PPS) n=4 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Mean Trough Plasma Concentration at 3rd Level for Age Range ≥12 to <16 Years

1.117 ug/mL Standard Deviation 0.400

PRIMARY outcome

Timeframe: Day 21

Outcome measures

Measure

Brivaracetam (PPS) n=12 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Mean Max Plasma Concentration for Age Range ≥1 Month to <2 Years

2.071 ug/mL Interval 0.32 to 4.305

PRIMARY outcome

Timeframe: Day 21

Outcome measures

Measure

Brivaracetam (PPS) n=22 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Mean Max Plasma Concentration for Age Range ≥2 to <12 Years

2.673 ug/mL Interval 0.561 to 5.418

PRIMARY outcome

Timeframe: Day 21

Outcome measures

Measure

Brivaracetam (PPS) n=4 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Mean Max Plasma Concentration for Age Range ≥12 to <16 Years

2.861 ug/mL Interval 2.627 to 3.371

SECONDARY outcome

Timeframe: Baseline to end of the 3-week evaluation period

Outcome measures

Measure

Brivaracetam (PPS) n=99 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Number of Subjects With at Least One Treatment-emergent Adverse Event Reported During the 3-week Evaluation Period

66 participants

SECONDARY outcome

Timeframe: Baseline to end of the 3-week evaluation period

Outcome measures

Measure

Brivaracetam (PPS) n=80 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5

Number of Subjects With a 50 % Reduction in Seizures Based on Seizure Diary Data From Baseline to End of the 3-week Evaluation Period

17 participants

SECONDARY outcome

Timeframe: Baseline to the end of the 3-week evaluation period

Population: Although 99 subjects were in the Safety Set and confirmed to have taken at least one dose of BRV, details on study drug intake were not able to be collected for 2 subjects. Therefore compliance could only be calculated for 97 subjects.

Outcome measures

Measure	Brivaracetam (PPS) n=97 Participants Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5
Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period <80 %	5 participants
Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period 80 % to 120 %	90 participants
Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period >120 %	2 participants

Adverse Events

Brivaracetam (SS)

Serious events: 8 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brivaracetam (SS) n=99 participants at risk Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5
Gastrointestinal disorders Diarrhoea	1.0% 1/99 • Number of events 1 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
General disorders Pyrexia	1.0% 1/99 • Number of events 1 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Infections and infestations Otitis media	1.0% 1/99 • Number of events 1 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Infections and infestations Respiratory tract infection	1.0% 1/99 • Number of events 1 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Infections and infestations Toxoplasmosis	1.0% 1/99 • Number of events 1 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Investigations Cytomegalovirus test positive	1.0% 1/99 • Number of events 1 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Metabolism and nutrition disorders Dehydration	2.0% 2/99 • Number of events 2 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Nervous system disorders Convulsion	4.0% 4/99 • Number of events 4 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.

Other adverse events

Measure	Brivaracetam (SS) n=99 participants at risk Brivaracetam (BRV) was given as 2 equally divided oral doses twice daily (bid). The dosage was adjusted as following: For subjects ≥8 years: * 0.4 mg/kg bid for Week 1 * 0.8 mg/kg bid for Week 2 * 1.6 mg/kg bid for Week 3 For subjects \<8 years: * 0.5 mg/kg bid for Week 1 * 1.0 mg/kg bid for Week 2 * 2.0 mg/kg bid for Week 3 Down-titration period (up to 2 weeks): For subjects ≥8 years: * 0.8 mg/kg bid for Week 4 * 0.4 mg/kg bid for Week 5 For subjects \<8 years: * 1.0 mg/kg bid for Week 4 * 0.5 mg/kg bid for Week 5
General disorders Irritability	8.1% 8/99 • Number of events 9 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
General disorders Pyrexia	7.1% 7/99 • Number of events 8 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
General disorders Fatigue	5.1% 5/99 • Number of events 5 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Infections and infestations Pharyngotonsillitis	5.1% 5/99 • Number of events 5 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Metabolism and nutrition disorders Decreased appetite	7.1% 7/99 • Number of events 7 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Nervous system disorders Somnolence	8.1% 8/99 • Number of events 9 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
Nervous system disorders Convulsion	6.1% 6/99 • Number of events 7 • Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study up to day 49. The Safety Set is all enrolled subjects who took at least 1 dose of study drug. Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.

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.
• Publication restrictions are in place

Restriction type: OTHER