Nonconvulsive Electrographic Seizures
Conditions
Keywords
Brivaracetam, Phenytoin, Nonconvulsive electrographic seizures
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.
Interventions
DRUGBrivaracetam intravenous solution
* Active Substance: Brivaracetam * Pharmaceutical Form: Solution for infusion * Concentration: 10 mg/mL * Route of Administration: Intravenous bolus use
DRUGBrivaracetam 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
DRUGPhenytoin intravenous solution
* Active Substance: Phenytoin * Pharmaceutical Form: Solution for infusion * Concentration: 50 mg/mL * Route of Administration: Intravenous use
DRUGPhenytoin oral tablets
* Active Substance: Phenytoin * Pharmaceutical Form: Tablet * Concentration: Weight based * Route of Administration: Oral use
Sponsors
PRA Health Sciences
UCB BIOSCIENCES, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Time to Achievement of 12 Hours of Seizure Freedom Relative to the Start of the First Acute Intravenous (iv) Administration | From start of first acute iv administration on Day 1 | 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 | 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. |
| 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 | From start of first acute iv administration | Seizure cessation is based on cEEG/vEEG (continuous video electroencephalogram) monitoring. |
Countries
United States
Participant flow
Recruitment details
Sixty subjects were planned to be screened in order to enroll 50 subjects in a 1:1 ratio to intravenous (iv) Brivaracetam (BRV) or iv Phenytoin (PHT) with stratification based on categorized age (\<65 years versus ≥65 years) across approximately 15 sites.
Pre-assignment details
This study was stopped due to low enrollment; the termination date was 17 Nov 2014. One subject enrolled, but discontinued from the study prematurely due to lack of efficacy.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
Baseline characteristics
| Characteristic | Brivaracetam |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 18 years STANDARD_DEVIATION 0 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
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.
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)
Population: This variable was not analyzed and no results are available.
Secondary
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
Population: This variable was not analyzed and no results are available.
Secondary
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 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)
Population: This variable was not analyzed and no results are available.
Secondary
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 frame: From start of first acute iv administration on Day 1
Population: This variable was not analyzed and no results are available.
Secondary
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.
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)
Population: This variable was not analyzed and no results are available.
Secondary
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.
Time frame: From start of first acute iv administration
Population: This variable was not analyzed and no results are available.