A Study to Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures
Condition: Electroencephalographic Neonatal Seizures
MeSH terms: Seizures
Intervention: Brivaracetam (BRV) intravenous (iv); Brivaracetam (BRV) oral
Intervention description: Exploratory Cohort:
Subjects will be dosed with BRV (0.5 mg/kg twice daily (bid)) according to the sites standard procedures. Treatment with 1 or more of the following antiepileptic drugs (AEDs): phenobarbital (PB), midazolam (MDZ), phenytoin (PHT), levetiracetam (LEV), or lidocaine (LDC) (first-line, second-line, or subsequent treatment) will continue in parallel with BRV treatment.
Confirmatory Cohort:
For subjects who enter the Confirmatory Cohorts, for the strength of BRV 1 mg/kg bid (2 mg/kg/day) has been determined based on the Pharmacokinetic (PK) findings of the Exploratory Cohort. Based on further monitoring of PK and safety findings dosing may be adjusted as new data are available. Administration of BRV is proposed as approximately 15-minute intravenous (iv) infusions. Treatment with previous antiepileptic drugs is permitted to continue if the subject is on a stable dose from 1 hour prior to initiation of the BRV treatment.; Subjects can switch from intravenous (iv) to oral brivaracetam (BRV) at any time during the BRV Extension Period
Intervention MeSH terms: Brivaracetam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 1 Day
Maximum age: 28 Days
Healthy volunteers: No
Keywords: Electroencephalographic neonatal seizures; Brivaracetam; Epilepsy; ENS; Newborns; Pharmacokinetic

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.
    

Eligibility criteria:

        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