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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by UCB, Inc.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc. ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier:
NCT02088957
First received: February 20, 2014
Last updated: July 14, 2014
Last verified: July 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, Inc.:

Primary Outcome Measures:
  • Percentage of subjects with seizure freedom for 12 hours starting 1 hour 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 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 continuous video electroencephalogram (vEEG) monitoring.


Secondary Outcome Measures:
  • Percentage of subjects with seizure freedom for 12 hours starting 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 video electroencephalogram (vEEG) 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 continuous electroencephalogram (cEEG) 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 continuous electroencephalogram (cEEG) 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 continuous electroencephalogram (cEEG) monitoring.


Estimated Enrollment: 50
Study Start Date: March 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: February 2017 (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 acute dose of BRV 100 mg can be given no sooner than 15 minutes after the first dose. If the second acute dose is not needed 12 hours after first acute iv dose, BRV will be continued as approximately 100 mg iv dose every 12 hours. The daily dose can be adapted according to investigator's clinical judgment, not exceeding a maximum dose of 400 mg per day for the first 24 hours of treatment. The rate of bolus administration is 50 mg (5 mL) undiluted BRV/min. On Day 5 (or earlier), based on tolerability), subjects will transition from iv to oral formulation, at comparable dosing for a maximum of 6 months. If subjects require further iv BRV treatment, iv BRV will be continued in the follow up treatment period 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

Acute intravenous (iv) dose of Brivaracetam (BRV) 200 mg as a bolus is administered on Day 1. If seizures recur, a second acute dose of 100 mg can be given no sooner than 15 minutes after the first dose. BRV is then continued as approximately 100 mg iv dose every 12 hours for up to 5 days for subjects who can switch to oral dose. Daily dose can be adapted not exceeding a maximum dose of 400 mg per day for first 24 hours of treatment.

BRV iv treatment can continue up to 6 months; daily dose can be adapted, not exceeding a maximum dose of BRV 200 mg per day.

Drug: Brivaracetam oral tablets

Oral Brivaracetam (BRV) 10 mg and 25 mg film-coated tablets, administered at a 1:1 ratio with current iv dosing regimen for up to 6 months.

Daily dose can be adapted according to the clinical judgment of the investigator, not exceeding a maximum dose of BRV 200 mg per day.

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 Day 5 (or earlier, based on tolerability), subjects will transition from iv to oral formulation at comparable dosing for a maximum of 6 months. If subject requires further iv PHT treatment, iv PHT will be continued in the follow up treatment period 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

Acute intravenous (iv) dose of Phenytoin (PHT) 20 mg/kg at a rate of 50 mg/min is administered on Day 1. If seizures recur, a second acute dose can be given no sooner than 15 minutes after the first dose to maintain unbound serum levels within the range of 1 to 2 mg/L. PHT is then continued with at least 2 daily divided doses according to site practice for up to 5 days for subjects who can switch to oral dose.

PHT iv treatment can continue up to 6 months; daily dose can be adapted.

Drug: Phenytoin oral tablets

Oral Phenytoin (PHT) tablets administered at a 1:1 ratio with current iv dosing regimen for up to 6 months.

Daily dose can be adapted according to the clinical judgment of the investigator.


  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 and having Nonconvulsive Electrographic Seizures (NCES) confirmed by continuous Electroencephalogram (cEEG), 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 NICU for at least 36 hours

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)
  • 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 Recruiting
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.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB, Inc. ( 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: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by UCB, Inc.:
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
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014