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

Phase 2
Completed
Conditions
Epilepsy
Interventions
Registration Number
NCT03405714
Lead Sponsor
UCB Biopharma S.P.R.L.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BrivaracetamBrivaracetamBrivaracetam 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.
Primary Outcome Measures
NameTimeMethod
Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 MinutesBlood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 MinutesBlood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 MinutesBlood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 MinutesBlood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 MinutesBlood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 MinutesBlood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 MinutesBlood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 MinutesBlood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 MinutesBlood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- BolusBlood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- BolusBlood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- BolusBlood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- BolusAt <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- BolusAt 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- BolusAt 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- BolusBlood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- BolusBlood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- BolusBlood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

Number of Participants With Adverse Events (AEs)From Screening until last visit (up to Day 68)

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.

Number of Participant Withdrawals Due to Adverse EventsFrom 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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (17)

Ep0065 210

🇭🇺

Budapest, Hungary

Ep0065 247

🇭🇺

Budapest, Hungary

Ep0065 502

🇨🇿

Hradec Králové, Czechia

Ep0065 264

🇮🇹

Milan, Italy

Ep0065 254

🇩🇪

Bielefeld, Germany

Ep0065 242

🇩🇪

Berlin, Germany

Ep0065 252

🇺🇸

Bronx, New York, United States

Ep0065 237

🇺🇸

Durham, North Carolina, United States

Ep0065 240

🇨🇿

Praha 4, Czechia

Ep0065 224

🇭🇺

Budapest, Hungary

Ep0065 222

🇭🇺

Debrecen, Hungary

Ep0065 238

🇮🇹

Pavia, Italy

Ep0065 232

🇭🇺

Miskolc, Hungary

Ep0065 223

🇲🇽

Aguas Calientes, Mexico

Ep0065 239

🇮🇹

Pavia, Italy

Ep0065 248

🇪🇸

Sevilla, Spain

Ep0065 230

🇮🇹

Roma, Italy

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