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

• ClinicalTrials.gov Identifier: NCT02088957
• Recruitment Status: Terminated
• First Posted: March 17, 2014
• Results First Posted: April 13, 2016
• Last Update Posted: July 11, 2018
• Sponsor: UCB BIOSCIENCES, Inc.
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES, Inc. )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Nonconvulsive Electrographic Seizures
• Interventions: Drug: Brivaracetam intravenous solution; Drug: Brivaracetam oral tablets; Drug: Phenytoin intravenous solution; Drug: Phenytoin oral tablets
• Enrollment: 1

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.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Period Title: Overall Study
Started	1	0
Completed	0	0
Not Completed	1	0
Reason Not Completed
Lack of Efficacy	1	0

Baseline Characteristics

Arm/Group Title		Brivaracetam
Arm/Group 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.
Overall Number of Baseline Participants		1
Baseline Analysis Population Description		Demographics of the only subject included are presented below.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 100.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1 participants
		18 (0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Female	1 100.0%
	Male	0 0.0%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

This variable was not analyzed and no results are available.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

This variable was not analyzed and no results are available.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

This variable was not analyzed and no results are available.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

4. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

This variable was not analyzed and no results are available.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

5. Secondary Outcome

Title	Percentage of Subjects Requiring a Second Acute Intravenous (iv) Administration Between 15 Minutes to 12 Hours After First Acute iv Administration
Description	[Not Specified]
Time Frame	Between 15 minutes to 12 hours after first acute iv administration

Outcome Measure Data

Analysis Population Description

This variable was not analyzed and no results are available.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

This variable was not analyzed and no results are available.

Arm/Group Title	Brivaracetam	Phenytoin
Arm/Group 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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Adverse Events were collected during the 75 days the only subject was included in this study.
Adverse Event Reporting Description	Adverse Events of the only subject included are presented below.
Arm/Group Title	Brivaracetam		Phenytoin
Arm/Group 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.
All-Cause Mortality
	Brivaracetam		Phenytoin
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Brivaracetam		Phenytoin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)		0/0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Brivaracetam		Phenytoin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		0/0
Gastrointestinal disorders
Constipation * 1	1/1 (100.00%)	1	0/0	0
General disorders
iv infiltration * 1	1/1 (100.00%)	1	0/0	0
Investigations
Decreased urinary output * 1	1/1 (100.00%)	1	0/0	0
Metabolism and nutrition disorders
Decreased appetite * 1	1/1 (100.00%)	1	0/0	0
Failure to thrive * 1	1/1 (100.00%)	1	0/0	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB (Study Director)
• Organization: UCB Clinical Trial Call Center
• Phone: +1 887 822 9493

• Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
• ClinicalTrials.gov Identifier: NCT02088957
• Other Study ID Numbers: N01394
• First Submitted: February 20, 2014
• First Posted: March 17, 2014
• Results First Submitted: March 14, 2016
• Results First Posted: April 13, 2016
• Last Update Posted: July 11, 2018