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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by UCB Pharma
Sponsor:
Collaborator:
PRA International
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier:
NCT02088957
First received: February 20, 2014
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Nonconvulsive Electrographic Seizures
Drug: Brivaracetam intravenous solution
Drug: Brivaracetam oral tablets
Drug: Phenytoin intravenous solution
Drug: Phenytoin oral tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.

  • 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 ] [ Designated as safety issue: No ]
    Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.

  • 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) ] [ Designated as safety issue: No ]
    Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    Seizure cessation is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.


Estimated Enrollment: 50
Study Start Date: March 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02088957

Contacts
Contact: UCB Clinical Trial Call Center +1 877 822 9493

Locations
United States, Kentucky
3 Recruiting
Lexington, Kentucky, United States
United States, Maryland
7 Recruiting
Baltimore, Maryland, United States
United States, Mississippi
1 Recruiting
Jackson, Mississippi, United States
United States, Ohio
9 Recruiting
Cleveland, Ohio, United States
2 Withdrawn
Columbus, Ohio, United States
United States, Pennsylvania
10 Recruiting
Philadelphia, Pennsylvania, United States
8 Recruiting
Pittsburgh, Pennsylvania, United States
Sponsors and Collaborators
UCB BIOSCIENCES, Inc.
PRA International
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier: NCT02088957     History of Changes
Other Study ID Numbers: N01394, 2012-001359-37
Study First Received: February 20, 2014
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by UCB Pharma:
Brivaracetam
Phenytoin
Nonconvulsive electrographic seizures

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Pharmaceutical Solutions
Phenytoin
Therapeutic Uses
Pharmacologic Actions
Anticonvulsants
Central Nervous System Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014