A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Intravenous Brivaracetam in Subjects >= 1 Month to < 16 Years of Age With Epilepsy

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03405714
• Collaborator: (none)
• Enrollment: 50
• Locations: 17
• Arm: 1
• Actual Duration (Months): 29.1
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Brivaracetam	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Intravenous Brivaracetam in Subjects >= 1 Month < 16 Years of Age With Epilepsy
• Actual Study Start Date: Jun 1, 2018
• Actual Primary Completion Date: Nov 4, 2020
• Actual Study Completion Date: Nov 4, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Brivaracetam Brivaracetam will be administered to various age-based cohorts. Cohort 1: Subjects >=12 to <16 years; Cohort 2: Subjects >=6 to <12 years; Cohort 3: Subjects >=2 to <6 years; Cohort 4: Subjects 1 month to <2 years. Enrollment will be sequential by descending age beginning with Cohort 1. For each cohort, the first half will receive a 15-minute iv infusion. The Data Monitoring Committee (DMC) will then review safety and, as available, PK data to make the following recommendations: the progression of the current cohort (up to 2-minute iv bolus infusion) and progression to initiate enrollment in the preceding cohort.

Drug: Brivaracetam; Pharmaceutical form: Solution for iv injection Route of administration: intravenous use Concentration: 10 mg/ml; Other Names: Briviact

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 16 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ep0065 252	Bronx	New York	United States	10467
2	Ep0065 237	Durham	North Carolina	United States	27710
3	Ep0065 502	Hradec Králové		Czechia
4	Ep0065 240	Praha 4		Czechia
5	Ep0065 242	Berlin		Germany
6	Ep0065 254	Bielefeld		Germany
7	Ep0065 210	Budapest		Hungary
8	Ep0065 224	Budapest		Hungary
9	Ep0065 247	Budapest		Hungary
10	Ep0065 222	Debrecen		Hungary
11	Ep0065 232	Miskolc		Hungary
12	Ep0065 264	Milan		Italy
13	Ep0065 238	Pavia		Italy
14	Ep0065 239	Pavia		Italy
15	Ep0065 230	Roma		Italy
16	Ep0065 223	Aguas Calientes		Mexico
17	Ep0065 248	Sevilla		Spain

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study Documents (Full-Text)

• Study Protocol - Jun 19, 2019
• Statistical Analysis Plan - Sep 25, 2020

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT03405714
• Other Study ID Numbers: EP0065; 2016-002452-25
• First Posted: Jan 23, 2018
• Last Update Posted: May 11, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by UCB Biopharma S.P.R.L.: Epilepsy; Brivaracetam; Briviact; Open-label; pediatric; intravenous
• Additional relevant MeSH terms: Epilepsy; Brivaracetam

Study Results

Participant Flow

Recruitment Details	The study started to enroll participants in June 2018 and concluded in November 2020.
Pre-assignment Detail	Participant Flow refers to the Safety Set-Intravenous (SS-iv).

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
STARTED	12	12	13	13
COMPLETED	12	12	13	13
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Overall Participants	12	12	13	13	50
Age (Count of Participants)
<=18 years	12 100%	12 100%	13 100%	13 100%	50 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.08 (1.16)	8.33 (1.61)	3.85 (0.99)	0.95 (0.59)	6.39 (4.76)
Sex: Female, Male (Count of Participants)
Female	6 50%	8 66.7%	5 38.5%	5 38.5%	24 48%
Male	6 50%	4 33.3%	8 61.5%	8 61.5%	26 52%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaskan Native	0 0%	0 0%	0 0%	2 15.4%	2 4%
Black	1 8.3%	0 0%	0 0%	0 0%	1 2%
White	11 91.7%	12 100%	13 100%	11 84.6%	47 94%

Outcome Measures

1. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	12	10	10	9
Geometric Mean (95% Confidence Interval) [nanograms per milliliter (ng/mL)]	149.0	NA	NA	310.6

2. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	12	10	8	10
Geometric Mean (95% Confidence Interval) [ng/mL]	1844.6	2058.8	1774.9	1566.6

3. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	12	10	11	9
Geometric Mean (95% Confidence Interval) [ng/mL]	1260.6	1189.5	1225.3	1341.7

4. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	0	3	0	0
Geometric Mean (95% Confidence Interval) [ng/mL]	290.5

5. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	0	3	0	0
Geometric Mean (95% Confidence Interval) [ng/mL]	2084.3

6. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	0	3	0	0
Geometric Mean (95% Confidence Interval) [ng/mL]	1149.8

7. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	0	1	2	3
Geometric Mean (95% Confidence Interval) [ng/mL]	466.0	204.5	482.9

8. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	0	1	3	3
Geometric Mean (95% Confidence Interval) [ng/mL]	2890.0	1948.8	2072.4

9. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Age Cohort: >=12 to <16 Years (PK-PPS)	Age Cohort: >=6 to <12 Years (PK-PPS)	Age Cohort: >=2 to <6 Years (PK-PPS)	Age Cohort : >=1 Month to <2 Years (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the Pharmacokinetic Per-protocol Set (PK-PPS).	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 as a bolus (up to 2-minute infusion). Participants formed the PK-PPS.
Measure Participants	0	1	2	3
Geometric Mean (95% Confidence Interval) [ng/mL]	1820	1203.5	727.4

10. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	19
Geometric Mean (95% Confidence Interval) [ng/mL]	NA

11. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	21
Geometric Mean (95% Confidence Interval) [ng/mL]	1903.0

12. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	21
Geometric Mean (95% Confidence Interval) [ng/mL]	1130.3

13. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	3
Geometric Mean (95% Confidence Interval) [ng/mL]	290.5

14. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	3
Geometric Mean (95% Confidence Interval) [ng/mL]	2084.3

15. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	3
Geometric Mean (95% Confidence Interval) [ng/mL]	1149.8

16. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	3
Geometric Mean (95% Confidence Interval) [ng/mL]	776.0

17. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	4
Geometric Mean (95% Confidence Interval) [ng/mL]	2697.8

18. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 Minutes
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	15-minute Infusion (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6 days). 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. Participants formed the PK-PPS.
Measure Participants	4
Geometric Mean (95% Confidence Interval) [ng/mL]	1030.0

19. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	22
Geometric Mean (95% Confidence Interval) [ng/mL]	120.5

20. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	19
Geometric Mean (95% Confidence Interval) [ng/mL]	1704.8

21. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	21
Geometric Mean (95% Confidence Interval) [ng/mL]	1383.9

22. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	0

23. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	0

24. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	0

25. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	3
Geometric Mean (95% Confidence Interval) [ng/mL]	167.5

26. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	3
Geometric Mean (95% Confidence Interval) [ng/mL]	1531.8

27. Primary Outcome

Title	Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- Bolus
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Bolus (PK-PPS)
Arm/Group Description	Participants received iv administration of BRV every 12 hours during the IV PK Period (1-6days). 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 second half received the bolus (up to 2-minute infusion). Participants formed PK-PPS.
Measure Participants	2
Geometric Mean (95% Confidence Interval) [ng/mL]	949.5

28. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

The SS-iv included study participants who received at least 1 dose of iv BRV.

Arm/Group Title	Age Cohort: >=12 to <16 Years (SS-iv)	Age Cohort: >=6 to <12 Years (SS-iv)	Age Cohort: >=2 to <6 Years (SS-iv)	Age Cohort: >=1 Month to <2 Years (SS-iv)
Arm/Group Description	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. Participants formed the Safety Set-Intravenous (SS-iv).	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. Participants formed the SS-iv.	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. Participants formed the Safety SS-iv.	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. Participants formed the SS-iv.
Measure Participants	12	12	13	13
Count of Participants [Participants]	3 25%	4 33.3%	7 53.8%	2 15.4%

29. Primary Outcome

Title	Number of Participant Withdrawals Due to Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

The SS-iv included study participants who received at least 1 dose of iv BRV.

Arm/Group Title	Age Cohort: >=12 to <16 Years (SS-iv)	Age Cohort: >=6 to <12 Years (SS-iv)	Age Cohort: >=2 to <6 Years (SS-iv)	Age Cohort: >=1 Month to <2 Years (SS-iv)
Arm/Group Description	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. Participants formed the Safety Set-Intravenous (SS-iv).	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. Participants formed the SS-iv.	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. Participants formed the Safety SS-iv.	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. Participants formed the SS-iv.
Measure Participants	12	12	13	13
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	From Screening until last visit (up to Day 68)
Arm/Group Title	Age Cohort: >=12 to <16 Years (SS-iv)		Age Cohort: >=6 to <12 Years (SS-iv)		Age Cohort: >=2 to <6 Years (SS-iv)		Age Cohort: >=1 Month to <2 Years (SS-iv)
Arm/Group Description	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. Participants formed the Safety Set-Intravenous (SS-iv).		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. Participants formed the SS-iv.		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. Participants formed the Safety SS-iv.		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. Participants formed the SS-iv.
All Cause Mortality
	Age Cohort: >=12 to <16 Years (SS-iv)		Age Cohort: >=6 to <12 Years (SS-iv)		Age Cohort: >=2 to <6 Years (SS-iv)		Age Cohort: >=1 Month to <2 Years (SS-iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/13 (0%)
Serious Adverse Events
	Age Cohort: >=12 to <16 Years (SS-iv)		Age Cohort: >=6 to <12 Years (SS-iv)		Age Cohort: >=2 to <6 Years (SS-iv)		Age Cohort: >=1 Month to <2 Years (SS-iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/13 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Age Cohort: >=12 to <16 Years (SS-iv)		Age Cohort: >=6 to <12 Years (SS-iv)		Age Cohort: >=2 to <6 Years (SS-iv)		Age Cohort: >=1 Month to <2 Years (SS-iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		4/12 (33.3%)		7/13 (53.8%)		2/13 (15.4%)
Gastrointestinal disorders
Vomiting	0/12 (0%)	0	1/12 (8.3%)	1	0/13 (0%)	0	0/13 (0%)	0
General disorders
Fatigue	0/12 (0%)	0	1/12 (8.3%)	1	1/13 (7.7%)	1	0/13 (0%)	0
Pyrexia	0/12 (0%)	0	0/12 (0%)	0	2/13 (15.4%)	2	0/13 (0%)	0
Vessel puncture site haemorrhage	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Infections and infestations
Conjunctivitis	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Ear infection	0/12 (0%)	0	0/12 (0%)	0	2/13 (15.4%)	2	0/13 (0%)	0
Nasopharyngitis	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Pharyngitis	1/12 (8.3%)	1	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0
Upper respiratory tract infection	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Nervous system disorders
Dizziness	2/12 (16.7%)	2	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0
Somnolence	0/12 (0%)	0	0/12 (0%)	0	2/13 (15.4%)	2	1/13 (7.7%)	1
Psychiatric disorders
Aggression	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Insomnia	0/12 (0%)	0	1/12 (8.3%)	1	0/13 (0%)	0	0/13 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/12 (0%)	0	1/12 (8.3%)	1	0/13 (0%)	0	0/13 (0%)	0
Rash	0/12 (0%)	0	1/12 (8.3%)	1	1/13 (7.7%)	1	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.