Epilepsy
Conditions
Keywords
Epilepsy, Brivaracetam, Briviact, Open-label, pediatric, intravenous
Brief summary
The purpose of the study is to evaluate the pharmacokinetics (PK), safety, and tolerability of brivaracetam (BRV) administered intravenously (iv) in subjects \>= 1 month to \< 16 years of age with epilepsy.
Interventions
DRUGBrivaracetam
* Pharmaceutical form: Solution for iv injection * Route of administration: intravenous use * Concentration: 10 mg/ml
Sponsors
UCB Biopharma S.P.R.L.
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
* Male or female from \>= 1 month to \< 16 years of age. For subjects who are \< 1 year from birth and who were preterm infants, the corrected gestational age should be used for this entry requirement * Weight \>= 3 kg (6.6 lbs) * Diagnosis of epilepsy * Acceptable candidate for venipuncture and intravenous (iv) infusion * Treatment with \>=1 anti epileptic drug (AED; including BRV) without a change of dose regimen for at least 7 days prior to Screening * No treatment with vagus nerve stimulation (VNS), OR the subject is being treated with VNS and the settings have been constant for \>=7 days prior to Screening * For female subjects: not of childbearing potential, OR of childbearing potential and not sexually active/negative pregnancy test, OR of childbearing potential and sexually active/negative pregnancy test/uses medically acceptable contraceptive methods
Exclusion criteria
* Subject has previously received iv Brivaracetam (BRV) in this study * Subject is being treated with BRV at a dose \>5mg/kg/day (rounded) or \>200mg/day for subjects with body weights \>40kg * Subject requires or is likely to require a change in concomitant antiepileptic drug(s) (AED\[s\]), dose of concomitant AED(s), or formulation of AED(s) during the 7 days prior to the intravenous (iv) pharmacokinetic (PK) Period * Subject is likely, in the opinion of the Investigator, to require rescue medication during the Initiating Oral BRV (IOB) Treatment or iv PK Periods * Subject has experienced generalized convulsive status epilepticus in the 28 days prior to Screening or during the Screening Period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 Minutes | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 Minutes | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 Minutes | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 Minutes | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 Minutes | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 Minutes | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 Minutes | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 Minutes | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 Minutes | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- Bolus | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- Bolus | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- Bolus | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- Bolus | At <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- Bolus | At 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- Bolus | At 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- Bolus | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- Bolus | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- Bolus | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration. |
| Number of Participants With Adverse Events (AEs) | From Screening until last visit (up to Day 68) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. |
| Number of Participant Withdrawals Due to Adverse Events | From Screening until last visit (up to Day 68) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. |
Countries
Czechia, Germany, Hungary, Italy, Mexico, Spain, United States
Participant flow
Recruitment details
The study started to enroll participants in June 2018 and concluded in November 2020.
Pre-assignment details
Participant Flow refers to the Safety Set-Intravenous (SS-iv).
Participants by arm
| Arm | Count |
|---|---|
| Age Cohort: >=12 to <16 Years Screening Period (1-10 days): Participants receiving open-label BRV (OLB) or prescribed oral BRV (RxB) continued to receive oral BRV. IOB Treatment Period (2-10 days): Participants who initiated Oral BRV (IOB) continued with oral BRV 2 milligram/kilogram/day (mg/kg/day). IV PK (Intravenous Pharmacokinetic) Period (1-6 days): During iv PK Period, iv BRV was administered every 12 hours. For OLB, RxB, and IOB participants, first iv Brivaracetam (BRV) dose was equivalent to final dose of oral BRV and for Initiating iv BRV (IIB) participants, first iv BRV dose was 1mg/kg. For each cohort, the first half received 15-minute infusion, the remaining half as a bolus (up to 2-minute infusion). Down-Titration Period: Participants who discontinued treatment, had their BRV dose reduced every week for a maximum of 4 weeks down to a dose of 1mg/kg/day. | 12 |
| Age Cohort: >=6 to <12 Years Screening Period (1-10 days): Participants receiving OLB or RxB continued to receive oral BRV. IOB Treatment Period (2-10 days): IOB Participants continued with oral BRV 2mg/kg/day. IV PK Period (1-6 days): During iv PK Period, iv BRV was administered every 12 hours. For OLB, RxB, and IOB participants, first iv BRV dose was equivalent to final dose of oral BRV and for IIB participants, first iv BRV dose was 1mg/kg. For each cohort, the first half received the 15-minute infusion, the remaining half as a bolus (up to 2-minute infusion). Down-Titration Period: Participants who discontinued treatment, had their BRV dose reduced every week for a maximum of 4 weeks down to a dose of 1mg/kg/day. | 12 |
| Age Cohort: >=2 to <6 Years Screening Period (1-10 days): Participants receiving OLB or RxB continued to receive oral BRV. IOB Treatment Period (2-10 days): IOB Participants continued with oral BRV 2mg/kg/day. IV PK Period (1-6 days): During iv PK Period, iv BRV was administered every 12 hours. For OLB, RxB, and IOB participants, first iv BRV dose was equivalent to final dose of oral BRV and for IIB participants, first iv BRV dose was 1mg/kg. For each cohort, the first half received the 15-minute infusion, the remaining half as a bolus (up to 2-minute infusion). Down-Titration Period: Participants who discontinued treatment, had their BRV dose reduced every week for a maximum of 4 weeks down to a dose of 1mg/kg/day. | 13 |
| Age Cohort: >=1 Month to <2 Years Screening Period (1-10 days): Participants receiving OLB or RxB continued to receive oral BRV. IOB Treatment Period (2-10 days): IOB Participants continued with oral BRV 2mg/kg/day. IV PK Period (1-6 days): During iv PK Period, iv BRV was administered every 12 hours. For OLB, RxB, and IOB participants, first iv BRV dose was equivalent to final dose of oral BRV and for IIB participants, first iv BRV dose was 1mg/kg. For each cohort, the first half received the 15-minute infusion, the remaining half as a bolus (up to 2-minute infusion). Down-Titration Period: Participants who discontinued treatment, had their BRV dose reduced every week for a maximum of 4 weeks down to a dose of 1mg/kg/day. | 13 |
| Total Title | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Age Cohort: >=12 to <16 Years | Age Cohort: >=6 to <12 Years | Age Cohort: >=2 to <6 Years | Age Cohort: >=1 Month to <2 Years | Total Title |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 12 Participants | 13 Participants | 13 Participants | 50 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.08 years STANDARD_DEVIATION 1.16 | 8.33 years STANDARD_DEVIATION 1.61 | 3.85 years STANDARD_DEVIATION 0.99 | 0.95 years STANDARD_DEVIATION 0.59 | 6.39 years STANDARD_DEVIATION 4.76 |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 12 Participants | 13 Participants | 11 Participants | 47 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 5 Participants | 5 Participants | 24 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 8 Participants | 8 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 3 / 12 | 4 / 12 | 7 / 13 | 2 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 13 | 1 / 13 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time frame: From Screening until last visit (up to Day 68)
Population: The SS-iv included study participants who received at least 1 dose of iv BRV.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Age Cohort: >=6 to <12 Years (PK-PPS) | Number of Participants With Adverse Events (AEs) | 4 Participants |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Number of Participants With Adverse Events (AEs) | 7 Participants |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Number of Participants With Adverse Events (AEs) | 2 Participants |
Primary
Number of Participant Withdrawals Due to Adverse Events
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time frame: From Screening until last visit (up to Day 68)
Population: The SS-iv included study participants who received at least 1 dose of iv BRV.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Number of Participant Withdrawals Due to Adverse Events | 0 Participants |
| Age Cohort: >=6 to <12 Years (PK-PPS) | Number of Participant Withdrawals Due to Adverse Events | 0 Participants |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Number of Participant Withdrawals Due to Adverse Events | 0 Participants |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Number of Participant Withdrawals Due to Adverse Events | 0 Participants |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 | 1844.6 ng/mL |
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 | 2058.8 ng/mL |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 | 1774.9 ng/mL |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 | 1566.6 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 Minutes | 1903.0 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- Bolus | 1704.8 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment. PK samples were not collected at Visit 4 in \>=12 to \<16 years, \>=2 to \<6 years, and \>=1 to \<2 years patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 | 2084.3 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 Minutes | 2084.3 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: At 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. PK samples were not collected at Visit 4 in bolus patients.
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment. PK samples were not collected at Visit 5 in \>=12 to \<16 years patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 | 2890.0 ng/mL |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 | 1948.8 ng/mL |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 | 2072.4 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 Minutes | 2697.8 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- Bolus | 1531.8 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 | 1260.6 ng/mL |
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 | 1189.5 ng/mL |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 | 1225.3 ng/mL |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 | 1341.7 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 Minutes | 1130.3 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- Bolus | 1383.9 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment. PK samples were not collected at Visit 4 in \>=12 to \<16 years, \>=2 to \<6 years, and \>=1 to \<2 years patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 | 1149.8 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 Minutes | 1149.8 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: At 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. PK samples were not collected at Visit 4 in bolus patients.
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment. PK samples were not collected at Visit 5 in \>=12 to \<16 years patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 | 1820 ng/mL |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 | 1203.5 ng/mL |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 | 727.4 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 Minutes | 1030.0 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- Bolus | 949.5 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 | 149.0 nanograms per milliliter (ng/mL) |
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 | NA nanograms per milliliter (ng/mL) |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 | NA nanograms per milliliter (ng/mL) |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 | 310.6 nanograms per milliliter (ng/mL) |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 Minutes | NA ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- Bolus | 120.5 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment. PK samples were not collected at Visit 4 in \>=12 to \<16 years, \>=2 to \<6 years, and \>=1 to \<2 years patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 | 290.5 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 Minutes | 290.5 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: At <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. PK samples were not collected at Visit 4 in bolus patients.
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment. PK samples were not collected at Visit 5 in \>=12 to \<16 years patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=6 to <12 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 | 466.0 ng/mL |
| Age Cohort: >=2 to <6 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 | 204.5 ng/mL |
| Age Cohort : >=1 Month to <2 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 | 482.9 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 Minutes
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 Minutes | 776.0 ng/mL |
Primary
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- Bolus
Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
Time frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)
Population: The PK-PPS included all study participants in the SS-iv having provided at least 1 measurable postdose plasma sample (with recorded sampling time) during the iv PK Period with documented iv BRV infusion times and without IPDs impacting the interpretability of the PK analyses. Here, N (number of participants analyzed) were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Age Cohort: >=12 to <16 Years (PK-PPS) | Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- Bolus | 167.5 ng/mL |