Efficacy Evaluation of Intravenous Brivaracetam and Phenytoin in Subjects With Nonconvulsive Electrographic Seizures

June 13, 2018 updated by: UCB BIOSCIENCES, Inc.

A Randomized, Open-label, Multicenter, Parallel-group, Exploratory Study to Evaluate the Efficacy of Intravenous Brivaracetam and Intravenous Phenytoin in Subjects Experiencing Nonconvulsive Electrographic Seizures

The primary objective of this study is to compare the efficacy of Brivaracetam and Phenytoin, both administered intravenously, in adult subjects experiencing nonconvulsive electrographic seizures.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Lexington, Kentucky, United States
        • 3
    • Mississippi
      • Jackson, Mississippi, United States
        • 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects ≥16 years. Subjects under 18 years may only be included where legally permitted and ethically accepted
  • Subjects in the neurological intensive care unit (NICU) (or equivalent closely monitored environment) having brain insult including traumatic brain injury and having nonconvulsive electrographic seizures (NCES) confirmed by electroencephalogram (EEG), lasting a minimum of 10 seconds but not >30 minutes (minimum of 1 seizure in the last 6 hours) and treatment with an antiepileptic drug (AED) is required according to the physician's clinical judgment
  • Subject is expected to be under cEEG monitoring with video surveillance in the Neuro ICU for at least 36 hours from the first administration of study drug

Exclusion Criteria:

  • Subject has history of severe adverse hematologic or cutaneous reaction to any drug
  • Subject presenting with status epilepticus or nonconvulsive status epilepticus (NCSE) (ie, 1 continuous, convulsive or nonconvulsive, unremitting seizure lasting >30 minutes during Visit 1)
  • Subject has been diagnosed with anoxic brain injury
  • Subject has a known history of status epilepticus during the 6 months preceding Visit 1
  • Subject is currently treated with Levetiracetam (LEV) or Phenytoin (PHT) or has been treated within the last 30 days before Visit 1 with LEV or PHT
  • Subject is on felbamate with <18 months' exposure before Visit 1
  • Subject has presence of any sign (clinical or imaging techniques) suggesting a rapidly progressing process such that the subject is not expected to survive >48 hours
  • Subject has any clinical condition that would impair reliable participation in the study or necessitate the use of medications not allowed by the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Brivaracetam

Subjects will receive an acute intravenous (iv) dose of Brivaracetam (BRV) 200 mg as a bolus on Day 1. If seizures recur, a second iv bolus of BRV 100 mg can be given no sooner than 15 minutes after the first bolus. If the second acute bolus is not needed within12 hours after first iv bolus, BRV will be continued as 100 mg iv dose every 12 hours (bid). The total dose for the first 24 hours of treatment should not exceed a maximum dose of 400 mg. The rate of bolus administration is 50 mg (5 mL) undiluted BRV/min. On study Day 5 (or earlier), subjects will transition from iv to oral formulation, at comparable dosing for a maximum of 6 months.

Subjects should transition to oral medication as soon as they are able to swallow tablets.
Drug: Brivaracetam intravenous solution
  • Active Substance: Brivaracetam
  • Pharmaceutical Form: Solution for infusion
  • Concentration: 10 mg/mL
  • Route of Administration: Intravenous bolus use
Drug: Brivaracetam oral tablets
  • Active Substance: Brivaracetam
  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 10 mg and 25 mg tablets; Daily Dose: 200 mg/day (100 mg bid)
  • Route of Administration: Oral use
Active Comparator: Phenytoin

Subjects will receive an acute intravenous (iv) dose of Phenytoin (PHT) 20 mg/kg at a rate of 50 mg/min on Day 1. If seizures recur, a second acute dose of PHT iv will be given no sooner than 15 minutes after the first dose. Treatment with PHT iv will be continued with at least 2 daily divided doses according to site practice. Daily PHT dose can be adapted according to investigator's clinical judgment. On study Day 5 (or earlier), subjects will transition from iv to oral formulation at comparable dosing for a maximum of 6 months.

Subjects should transition to oral medication as soon as they are able to swallow tablets.
Drug: Phenytoin intravenous solution
  • Active Substance: Phenytoin
  • Pharmaceutical Form: Solution for infusion
  • Concentration: 50 mg/mL
  • Route of Administration: Intravenous use
Drug: Phenytoin oral tablets
  • Active Substance: Phenytoin
  • Pharmaceutical Form: Tablet
  • Concentration: Weight based
  • Route of Administration: Oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With Seizure Freedom for 12 Hours Based on cEEG/vEEG Monitoring Which Starts 1 Hour After the End of the Last Acute iv Administration of Study Drug and Prior to the Initiation of Bid (Twice a Day) Dosing
Time Frame: From 1 hour after end of the last acute iv administration of study drug and prior to initiation of bid dosing (which begins 12 hours after the last acute iv administration of study drug)
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
From 1 hour after end of the last acute iv administration of study drug and prior to initiation of bid dosing (which begins 12 hours after the last acute iv administration of study drug)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With Seizure Freedom for 12 Hours Based on cEEG/vEEG Monitoring Which Starts After the End of the Last Acute Intravenous (iv) Administration of Study Drug and Prior to the Initiation of Bid (Twice a Day) Dosing
Time Frame: From end of the last acute iv administration of study drug and prior to initiation of bid dosing (which begins 12 hours after the last acute iv administration of study drug)
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
From end of the last acute iv administration of study drug and prior to initiation of bid dosing (which begins 12 hours after the last acute iv administration of study drug)
Time to Achievement of 12 Hours of Seizure Freedom Relative to the Start of the First Acute Intravenous (iv) Administration
Time Frame: From start of first acute iv administration on Day 1
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
From start of first acute iv administration on Day 1
Time to Achievement of 12 Hours of Seizure Freedom Relative to the Start of the Last Acute Intravenous (iv) Administration That Occurred Prior to the Initiation of Bid (Twice a Day) Dosing
Time Frame: From start of last acute iv administration prior to initiation of bid dosing (which begins 12 hours after the last acute iv administration of study drug)
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
From start of last acute iv administration prior to initiation of bid dosing (which begins 12 hours after the last acute iv administration of study drug)
Percentage of Subjects Requiring a Second Acute Intravenous (iv) Administration Between 15 Minutes to 12 Hours After First Acute iv Administration
Time Frame: Between 15 minutes to 12 hours after first acute iv administration
Between 15 minutes to 12 hours after first acute iv administration
Time to First Onset of Seizure Cessation Relative to the Start of the First Acute Intravenous (iv) Administration
Time Frame: From start of first acute iv administration
Seizure cessation is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
From start of first acute iv administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UCB BIOSCIENCES, Inc.

Collaborators

PRA Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

February 20, 2014

First Submitted That Met QC Criteria

March 13, 2014

First Posted (Estimate)

March 17, 2014

Study Record Updates

Last Update Posted (Actual)

July 11, 2018

Last Update Submitted That Met QC Criteria

June 13, 2018

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N01394

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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