A Study to Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures

UCB

Status and phase

Terminated

Phase 3

Conditions

Electroencephalographic Neonatal Seizures

Treatments

Drug: Brivaracetam (BRV) intravenous (iv)

Drug: Brivaracetam (BRV) oral

Study type

Interventional

Funder types

Industry

Identifiers

NCT03325439

N01349

2015-002756-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

9 patients

Sex

All

Ages

1 to 28 days old

Volunteers

No Healthy Volunteers

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