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

Primary Purpose

Nonconvulsive Electrographic Seizures

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Brivaracetam intravenous solution
Brivaracetam oral tablets
Phenytoin intravenous solution
Phenytoin oral tablets
Sponsored by
UCB BIOSCIENCES, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonconvulsive Electrographic Seizures focused on measuring Brivaracetam, Phenytoin, Nonconvulsive electrographic seizures

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 3
  • 1

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Brivaracetam

Phenytoin

Arm Description

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.

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.

Outcomes

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
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
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
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
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 to First Onset of Seizure Cessation Relative to the Start of the First Acute Intravenous (iv) Administration
Seizure cessation is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.

Full Information

First Posted
February 20, 2014
Last Updated
June 13, 2018
Sponsor
UCB BIOSCIENCES, Inc.
Collaborators
PRA Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02088957
Brief Title
Efficacy Evaluation of Intravenous Brivaracetam and Phenytoin in Subjects With Nonconvulsive Electrographic Seizures
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Terminated
Why Stopped
Termination of study due to low enrollment. There were no safety issues.
Study Start Date
March 2014 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB BIOSCIENCES, Inc.
Collaborators
PRA Health Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonconvulsive Electrographic Seizures
Keywords
Brivaracetam, Phenytoin, Nonconvulsive electrographic seizures

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brivaracetam
Arm Type
Experimental
Arm Description
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.
Arm Title
Phenytoin
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Brivaracetam intravenous solution
Intervention Description
Active Substance: Brivaracetam Pharmaceutical Form: Solution for infusion Concentration: 10 mg/mL Route of Administration: Intravenous bolus use
Intervention Type
Drug
Intervention Name(s)
Brivaracetam oral tablets
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Phenytoin intravenous solution
Intervention Description
Active Substance: Phenytoin Pharmaceutical Form: Solution for infusion Concentration: 50 mg/mL Route of Administration: Intravenous use
Intervention Type
Drug
Intervention Name(s)
Phenytoin oral tablets
Intervention Description
Active Substance: Phenytoin Pharmaceutical Form: Tablet Concentration: Weight based Route of Administration: Oral use
Primary Outcome Measure Information:
Title
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
Description
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
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)
Secondary Outcome Measure Information:
Title
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
Description
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
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)
Title
Time to Achievement of 12 Hours of Seizure Freedom Relative to the Start of the First Acute Intravenous (iv) Administration
Description
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
Time Frame
From start of first acute iv administration on Day 1
Title
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
Description
Seizure freedom is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
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)
Title
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
Title
Time to First Onset of Seizure Cessation Relative to the Start of the First Acute Intravenous (iv) Administration
Description
Seizure cessation is based on cEEG/vEEG (continuous video electroencephalogram) monitoring.
Time Frame
From start of first acute iv administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Clinical Trial Call Center
Organizational Affiliation
+1 877 822 9493 (UCB)
Official's Role
Study Director
Facility Information:
Facility Name
3
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
1
City
Jackson
State/Province
Mississippi
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

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

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