repeated electroencephalographic seizures
Conditions
Interventions
brivaracetam 10mg/ml - 5ml vial (sterile solution for intravenous infusion)
brivaracetam 10mg/ml - 300ml oral solution for use
BRIVARACETAM
ELECTROENCEPHALOGRAPHIC SEIZURES
NEONATES
Sponsors
UCB Pharma
Eligibility
Age
2 Years to 11 Years
Inclusion criteria
Inclusion criteria: 1. An Independent Ethics Committee (IEC)-approved written ICF is signed and dated by the parent(s) or legal representative(s). 2a. Confirmation on VEEG of *2 minutes of cumulative ENS or *3 identifiable ENS prior to entering the Evaluation Period (ENS is defined as a seizure lasting for at least 10 seconds on VEEG), despite receiving previous AED 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. 3. Subject is male or female and must be at least 34 weeks of CGA. In addition, term neonates up to 27 days of PNA and preterm neonates up to 40 weeks of PMA and 27 days of PNA can be enrolled. 4. Subject weighs at least 2.3kg at the time of enrollment. 5. Subjects with or without concomitant hypothermia treatment.
Exclusion criteria
Exclusion criteria: 1a. Subject receiving AED treatment other than PB, MDZ, PHT, LEV (*60mg/ kg/day), or LDC for the treatment of seizures prior to or at the time of enrollment (Confirmatory Cohorts only). 2. Subject with seizures responding to previous AED treatment immediately prior to BRV treatment, pyridoxine treatment, or correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia). 3. Subject requires extra corporeal membrane oxygenation. 4. Subject has seizures related to prenatal maternal drug use or drug withdrawal. 5. Subject has known severe disturbance of hemostasis, as assessed by the Investigator. 6. Subject has a poor prognosis for survival, as judged by the Investigator. 7a. 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 2mg/dL. 9. Subject requiring or expected to require phototherapy or exchange transfusion due to elevated bilirubin. 10. Subject with rapidly increasing bilirubin that may preclude the subject from inclusion in the study at the discretion of the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Plasma concentration of brivaracetam (BRV) 30-60 min after the BRV infusion on day 1 2. Plasma concentration of brivaracetam (BRV) 2-4 hours after the BRV infusion on day 1 3. Plasma concentration of brivaracetam (BRV) 8-12 hours after the BRV infusion on day 1 4. Plasma concentrations of BRV on other occasions 5. Plasma concentration of the BRV metabolite ucb-42145 (acid) 30-60 min after the BRV infusion on day 1 6. Plasma concentration of the BRV metabolite ucb-42145 (acid) 2-4 hours after the BRV infusion on day 1 7. Plasma concentration of the BRV metabolite ucb-42145 (acid) 8-12 hours after the BRV infusion on day 1 8. Plasma concentration of the BRV metabolite ucb-100406-1 (hydroxy) 30-60 min after the BRV infusion on day 1 9. Plasma concentration of the BRV metabolite ucb-100406-1 (hydroxy) 2-4 hours after the BRV infusion on day 1 10. Plasma concentration of the BRV metabolite ucb-100406-1 (hydroxy) 8-12 hours after the BRV infusion on day 1 11. Plasma concentration of the BRV metabolite ucb-107092-1 (hydroxyacid) 30-60 min after the BRV infusion on day 1 12. Plasma concentration of the BRV metabolite ucb-107092-1 (hydroxyacid) 2-4 hours after the BRV infusion on day 1 13. Plasma concentration of the BRV metabolite ucb-107092-1 (hydroxyacid) 8-12 hours after the BRV infusion on day 1 14. Area under the BRV plasma concentration time curve 15. Distribution volume of BRV 16. Plasma clearance of BRV 17. Plasma concentration of the concomitant antiepileptic drug phenobarbital AEDs if administered | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Percentage of responders to brivaracetam (BRV) treatment from Baseline to 3 hours after the initial BRV dose 2. Percentage of subjects with at least 80% reduction in nonsevere seizure burden from Baseline to 3 hours after the initial BRV treatment 3. Percentage of subjects with at least 50% reduction in severe seizure burden from Baseline to 3 hours after the initial BRV treatment 4. Absolute change in average seizure burden measured by continuous video-electroencephalography (VEEG) from Baseline to the end of the 96-hour Evaluation Period 5. Percent reduction in average seizure burden measured by continuous VEEG from Baseline to the end of the 96-hour Evaluation Period 6. Percentage of BRV responders at the end of the 96-hour Evaluation Period 7. Percentage of subjects who are seizure-free (100% reduction in seizure burden from Baseline) at 24 hours following the start of initial BRV treatment, categorized by subjects with nonsevere or severe seizure burden at Baseline 8. Time to reduction in seizure burden for BRV responders 9. Percentage of Subjects with Seizure Freedom at the end of Down-Titration Period 10. Percentage of Subjects with at least 50% reduction in electroencephalographic neonatal seizures (ENS) frequency per hour from Baseline to the end of the 96-hour Evaluation Period 11. Percentage of subjects who are seizure-free by time interval over the 96-hour evaluation period 12. Absolute change of clinical seizures correlated with continuous VEEG from Baseline to the end of the 96-hour Evaluation Period 13. Absolute change of clinical seizures correlated with continuous VEEG by time interval over the 96-hour evaluation period 14. Percentage of Subjects with clinical seizures correlated with continuous VEEG from Baseline to the end of the 96-hour Evaluation Period 15. Percentage of Subjects with clinical seizures correlated with continuous VEEG by time interval over the 96-hour evaluation period 16. Absolute change from Ba | — |
Countries
The Netherlands
Outcome results
None listed