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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Nonconvulsive Electrographic Seizures

Intervention / Treatment
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* Drug: Brivaracetam intravenous solution
* Drug: Brivaracetam oral tablets
* Drug: Phenytoin intravenous solution
* Drug: Phenytoin oral tablets


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brivaracetam<br>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<br>* Active Substance: Brivaracetam Pharmaceutical Form: Solution for infusion Concentration: 10 mg/mL Route of Administration: Intravenous bolus use<br>Drug: Brivaracetam oral tablets<br>* 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<br>|
| Active Comparator: Phenytoin<br>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<br>* Active Substance: Phenytoin Pharmaceutical Form: Solution for infusion Concentration: 50 mg/mL Route of Administration: Intravenous use<br>Drug: Phenytoin oral tablets<br>* Active Substance: Phenytoin Pharmaceutical Form: Tablet Concentration: Weight based Route of Administration: Oral use<br>|

What is the study measuring?
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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 | 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 | 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 | 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 | 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 |  | 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. | From start of first acute iv administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brivaracetam, Phenytoin, Nonconvulsive electrographic seizures