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

NCT ID: NCT03325439

Last Updated: 2024-04-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-07
• Study Completion Date: 2021-05-29

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.

Conditions

Electroencephalographic Neonatal Seizures

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Brivaracetam (BRV)

Exploratory Cohort and Confirmatory Cohorts

Group Type: EXPERIMENTAL

Brivaracetam (BRV) intravenous (iv)

Intervention Type: DRUG

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.

Brivaracetam (BRV) oral

Intervention Type: DRUG

Subjects can switch from intravenous (iv) to oral brivaracetam (BRV) at any time during the BRV Extension Period

Interventions

Brivaracetam (BRV) intravenous (iv)

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.

Intervention Type: DRUG

Brivaracetam (BRV) oral

Subjects can switch from intravenous (iv) to oral brivaracetam (BRV) at any time during the BRV Extension Period

Intervention Type: DRUG

Other Intervention Names

Briviact; Briviact

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Biopharma SRL

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

UCB Cares

Role: STUDY_DIRECTOR

UCB (+1 844 599 2273)

Locations

N01349 204

Leuven, , Belgium

N01349 205

Prague, , Czechia

N01349 207

Lille, , France

N01349 206

Paris, , France

N01349 218

Erlangen, , Germany

N01349 209

Freiburg im Breisgau, , Germany

N01349 211

Cork, , Ireland

N01349 212

Messina, , Italy

N01349 213

Parma, , Italy

N01349 256

Roma, , Italy

N01349 251

Cambridge, , United Kingdom

N01349 216

London, , United Kingdom

Countries

Belgium; Czechia; France; Germany; Ireland; Italy; United Kingdom

References

Pressler R, Boylan G, Dempsey E, Klotz KA, Krauwinkel W, Will E, Morita D, Floricel F, Elshoff JP, van den Anker J. Pharmacokinetics and safety of brivaracetam in neonates with repeated electroencephalographic seizures: A multicenter, open-label, single-arm study. Epilepsia Open. 2024 Apr;9(2):522-533. doi: 10.1002/epi4.12875. Epub 2024 Jan 11.

Reference Type: RESULT

PMID: 38049197 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.briviact.com/briviact-PI.pdf?v=1479491757

Product Information

http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

2015-002756-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

N01349

Identifier Type: -

Identifier Source: org_study_id