NCT03325439TerminatedPhase 3
A Multicenter, Open-Label, Single-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Neonates With Repeated Electroencephalographic Seizures
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- UCB Biopharma SRL
- Enrollment
- 9
- Locations
- 12
- Primary Endpoint
- Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1
Study Overview
Brief Summary
The purpose of the study is to evaluate the pharmacokinetics (PK) of brivaracetam (BRV) in neonates who have seizures that are not adequately controlled with previous antiepileptic drug (AED) treatment, and to identify the optimal BRV dose (Exploratory Cohort) for the treatment of subjects enrolled into the Confirmatory Cohorts of this study.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Day to 28 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Confirmation on video-electroencephalography (VEEG) of >= 2 minutes of cumulative electroencephalographic neonatal seizures (ENS), or >=3 identifiable ENS prior to entering the Evaluation Period, despite receiving previous antiepileptic drug treatment for the treatment of electroencephalographic seizures. The occurrence of ENS during an up to 1-hour period must be confirmed either by the local or central VEEG reader prior to drug administration. Preferably, the central VEEG reader should confirm the required ENS
- •Subject is male or female and must be at least 34 weeks of corrected gestational age (CGA). In addition, term neonates up to 27 days of postnatal age (PNA) and preterm neonates up to 40 weeks of CGA and 27 days of PNA can be enrolled
- •Subject weighs at least 2.3 kg at the time of enrollment
- •Subjects with or without concomitant hypothermia treatment
Exclusion Criteria
- •Subjects are not permitted to be enrolled in the study if any of the following criteria are met:
- •Subject receiving antiepileptic drug (AED) treatment other than phenobarbital, midazolam, phenytoin, levetiracetam (≤60 mg/kg/day), or lidocaine for the treatment of seizures prior to or at the time of enrollment (Confirmatory Cohorts only)
- •Subject with seizures responding to any of the following: previous AED treatment immediately prior to BRV treatment, pyridoxine treatment, or correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia)
- •Subject requires extra corporeal membrane oxygenation
- •Subject has seizures related to prenatal maternal drug use or drug withdrawal
- •Subject has known severe disturbance of hemostasis, as assessed by the Investigator
- •Subject has a poor prognosis for survival, as judged by the Investigator
- •Subject has 2x upper limit of normal (ULN) of any of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), with the following exception:
- •For subjects with perinatal asphyxia, elevation of AST, ALT or ALP <5x ULN is acceptable, if initial and peak elevation of liver function tests (LFTs) occurs within 5 days after birth, and the time course of LFT elevation is compatible with hepatic injury due to perinatal asphyxia. The determination of ULN will be based on the subject's gestational age (GA) and the site's normal range values for the respective GA
- •Subject has direct (conjugated) bilirubin levels >2 mg/dL
- •Subject requiring or expected to require phototherapy or exchange transfusion due to elevated bilirubin
- •Subject with rapidly increasing bilirubin that may preclude the subject from inclusion in the study at the discretion of the Investigator
Arms & Interventions
Brivaracetam (BRV)
Experimental
Exploratory Cohort and Confirmatory Cohorts
Intervention: Brivaracetam (BRV) intravenous (iv) (Drug)
Brivaracetam (BRV)
Experimental
Exploratory Cohort and Confirmatory Cohorts
Intervention: Brivaracetam (BRV) oral (Drug)
Outcomes
Primary Outcomes
Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1
Time Frame: Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1
Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1 to determine the BRV plasma concentration.
Secondary Outcomes
- Percentage of Responders to BRV Treatment From Baseline to 3 Hours After the Initial BRV Treatment(From Baseline to 3 hours after the initial BRV treatment)
- Percentage of Participants With at Least 80% Reduction in Nonsevere Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment(From Baseline to 3 hours after the initial BRV treatment)
- Percentage of BRV Responders at the End of the 96-hour Evaluation Period(From Baseline to the end of the 96-hour Evaluation Period)
- Percentage of Participants Who Are Seizure-free at 24 Hours Following the Start of Initial BRV Treatment, Categorized by Subjects With Nonsevere or Severe Seizure Burden at Baseline(From Baseline to 24 hours after the initial BRV treatment)
- Time to Reduction in Seizure Burden for BRV Responders(From Baseline to the first timepoint when BRV responder criteria are met (up to 96-hour Evaluation Period))
- Percentage of Participants With Seizure Freedom at the End of the Down-Titration Period(From Baseline to the end of the Down-Titration Period (up to 97 days))
- Percentage of Participants With at Least 50% Reduction in Electroencephalographic Neonatal Seizures (ENS) Frequency Per Hour From Baseline to the End of the 96-hour Evaluation Period(From Baseline to the end of the 96-hour Evaluation Period)
- Percentage of Participants With at Least 50% Reduction in Severe Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment(From Baseline to 3 hours after the initial BRV treatment)
- Absolute Change in Average Seizure Burden Measured by Continuous Video-electroencephalography (VEEG) From Baseline to the End of the 96-hour Evaluation Period(From Baseline to the end of the 96-hour Evaluation Period)
- Percentage Change in Average Seizure Burden Measured by Continuous VEEG From Baseline to the End of the 96-hour Evaluation Period(From Baseline to the end of the 96-hour Evaluation Period)
- Percentage of Participants Who Are Seizure-free by Time Interval Over the 96-hour Evaluation Period Following the Start of the Initial BRV Treatment(From 3 hours following the start of the initial BRV treatment to the end of the 96-hour Evaluation Period)
- Absolute Difference in Clinical Seizures at the End of the 24-hour Evaluation Period From Baseline for Neonates With Motor Seizures at the Time of Inclusion(From Baseline to the end of the 24-hour Evaluation Period)
- Percent Difference in Clinical Seizures at the End of the 24-hour Evaluation Period From Baseline for Neonates With Motor Seizures at the Time of Inclusion(From Baseline to the end of the 24-hour Evaluation Period)
- Percentage of Participants With Adverse Events (AEs) as Reported by the Investigator(Adverse Events were collected from Screening Period until the Safety Follow-Up Visit (up to Day 75))
Investigators
Study Sites (12)
Loading locations...
Similar Trials
Completed
Phase 1
A Study to Evaluate the Pharmacokinetics and Safety of Brivaracetam in Healthy Chinese SubjectsHealthy ParticipantsNCT04882540UCB Biopharma SRL12
Active, not recruiting
Phase 3
A Study to Test the Long-term Safety and Tolerability of Brivaracetam in Study Participants With Childhood Absence Epilepsy or Juvenile Absence EpilepsyChildhood Absence EpilepsyNCT06315322UCB Biopharma SRL70
Completed
Phase 3
A Study to Evaluate the Safety and Tolerability of Intravenous Brivaracetam (BRV) as Replacement for Oral Brivaracetam in Japanese Subjects >=16 Years of Age With Partial Seizures With or Without Secondary GeneralizationPartial Seizures With or Without Secondary GeneralizationEpilepsyNCT03685630UCB Biopharma S.P.R.L.10
Completed
Phase 3
A Study to Evaluate the Efficacy, Safety, and Tolerability of Brivaracetam as Monotherapy in Patients 2 to 25 Years of Age With Childhood Absence Epilepsy or Juvenile Absence EpilepsyJuvenile Absence EpilepsyChildhood Absence EpilepsyNCT04666610UCB Biopharma SRL153
Recruiting
Phase 3
A Study to Test the Safety and Tolerability of Brivaracetam in Children and Adolescents With SeizuresEpilepsyNCT04715646UCB Biopharma SRL70