Epilepsy
Conditions
Keywords
Brivaracetam, Epilepsy, Child, Pharmacokinetics, Adolescents
Brief summary
Initial study in children with epilepsy to evaluate the pharmacokinetics, safety, tolerability and preliminary efficacy of adjunctive treatment with brivaracetam, and to develop dosing adaptations for future studies.
Interventions
DRUGBrivaracetam
Oral solution Evaluation period (3 weeks up-titration): 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
Sponsors
UCB Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 16 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of epilepsy * Subject having at least 1 seizure (any type) during the 3 weeks before first visit * Stable dosing of 1-3 concomitant antiepileptic drugs
Exclusion criteria
* Pregnant or nursing females * Concomitant use of Levetiracetam * Epilepsy secondary to a Progressive cerebral disease/tumor or other neurodegenerative disease * History of status epilepticus * Clinically significant acute or chronic illness, underlying disease or medication condition * History of suicide attempt
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Max Plasma Concentration for Age Range ≥12 to <16 Years | Day 21 |
| Mean Trough Plasma Concentration at 3rd Level for Age Range ≥12 to <16 Years | Day 21 |
| Mean Max Plasma Concentration for Age Range ≥1 Month to <2 Years | Day 21 |
| Mean Max Plasma Concentration for Age Range ≥2 to <12 Years | Day 21 |
| Mean Trough Plasma Concentration at 3rd Level for Age Range ≥2 to <12 Years | Day 21 |
| Mean Trough Plasma Concentration at 3rd Level for Age Range ≥1 Month to <2 Years | Day 21 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Subjects With a 50 % Reduction in Seizures Based on Seizure Diary Data From Baseline to End of the 3-week Evaluation Period | Baseline to end of the 3-week evaluation period |
| Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period | Baseline to the end of the 3-week evaluation period |
| Number of Subjects With at Least One Treatment-emergent Adverse Event Reported During the 3-week Evaluation Period | Baseline to end of the 3-week evaluation period |
Countries
Belgium, Czechia, Mexico, Poland, Spain, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | AE, non-serious non-fatal | 5 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | SAE, non-fatal | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Brivaracetam (ES) |
|---|---|
| Age, Continuous | 6.3 years STANDARD_DEVIATION 4.8 |
| BMI | 17.1 kg/m^2 STANDARD_DEVIATION 3.4 |
| Height | 111.8 centimeters STANDARD_DEVIATION 32.9 |
| Racial Group Black or African American | 4 participants |
| Racial Group Other | 16 participants |
| Racial Group White | 80 participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 49 Participants |
| Weight | 24.2 kilograms STANDARD_DEVIATION 16.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 99 |
| serious Total, serious adverse events | 8 / 99 |
Outcome results
Primary
Mean Max Plasma Concentration for Age Range ≥12 to <16 Years
Time frame: Day 21
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Brivaracetam (PPS) | Mean Max Plasma Concentration for Age Range ≥12 to <16 Years | 2.861 ug/mL |
Primary
Mean Max Plasma Concentration for Age Range ≥1 Month to <2 Years
Time frame: Day 21
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Brivaracetam (PPS) | Mean Max Plasma Concentration for Age Range ≥1 Month to <2 Years | 2.071 ug/mL |
Primary
Mean Max Plasma Concentration for Age Range ≥2 to <12 Years
Time frame: Day 21
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Brivaracetam (PPS) | Mean Max Plasma Concentration for Age Range ≥2 to <12 Years | 2.673 ug/mL |
Primary
Mean Trough Plasma Concentration at 3rd Level for Age Range ≥12 to <16 Years
Time frame: Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brivaracetam (PPS) | Mean Trough Plasma Concentration at 3rd Level for Age Range ≥12 to <16 Years | 1.117 ug/mL | Standard Deviation 0.4 |
Primary
Mean Trough Plasma Concentration at 3rd Level for Age Range ≥1 Month to <2 Years
Time frame: Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brivaracetam (PPS) | Mean Trough Plasma Concentration at 3rd Level for Age Range ≥1 Month to <2 Years | 0.825 ug/mL | Standard Deviation 0.826 |
Primary
Mean Trough Plasma Concentration at 3rd Level for Age Range ≥2 to <12 Years
Time frame: Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brivaracetam (PPS) | Mean Trough Plasma Concentration at 3rd Level for Age Range ≥2 to <12 Years | 0.967 ug/mL | Standard Deviation 0.536 |
Secondary
Number of Subjects With a 50 % Reduction in Seizures Based on Seizure Diary Data From Baseline to End of the 3-week Evaluation Period
Time frame: Baseline to end of the 3-week evaluation period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam (PPS) | 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
Number of Subjects With at Least One Treatment-emergent Adverse Event Reported During the 3-week Evaluation Period
Time frame: Baseline to end of the 3-week evaluation period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam (PPS) | Number of Subjects With at Least One Treatment-emergent Adverse Event Reported During the 3-week Evaluation Period | 66 participants |
Secondary
Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brivaracetam (PPS) | Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period | <80 % | 5 participants |
| Brivaracetam (PPS) | Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period | >120 % | 2 participants |
| Brivaracetam (PPS) | Percent Compliance With Brivaracetam Oral Solution During the 3-week Evaluation Period | 80 % to 120 % | 90 participants |