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

Study Overview
=================
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.

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

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Drug: Brivaracetam


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brivaracetam<br>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<br>* Pharmaceutical form: Solution for iv injection Route of administration: intravenous use Concentration: 10 mg/ml<br>* Other names: Briviact;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | At <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | At 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | At 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | From Screening until last visit (up to Day 68) | 
| 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. | From Screening until last visit (up to Day 68) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) | 
| 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. | Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epilepsy, Brivaracetam, Briviact, Open-label, pediatric, intravenous