A Study to Assess the Efficacy and Safety of Brivaracetam as Treatment for Increased Seizure Activity in an Epilepsy Monitoring Unit Setting

A Multicenter, Open-Label, Randomized, Parallel-Group, Active-Controlled Study to Assess the Efficacy and Safety of Brivaracetam Administered Intravenously as Treatment for Increased Seizure Activity in an Epilepsy Monitoring Unit Setting

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03021018

Enrollment

Registered

2017-01-13

Start date

2017-02-06

Completion date

2018-04-27

Last updated

2020-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Epilepsy

Keywords

Epilepsy, Brivaracetam, Epilepsy Monitoring Unit, Increased seizure activity

Brief summary

The purpose of this study is to assess the efficacy of intravenous brivaracetam (BRV) compared to intravenous lorazepam (LZP) in subjects with epilepsy undergoing Epilepsy Monitoring Unit (EMU) evaluation who experience seizures that require prompt treatment.

Interventions

DRUGBrivaracetam

* Pharmaceutical Form: Solution for infusion * Concentration: 10 mg/ml * Route of Administration: intravenous

DRUGLorazepam

* Pharmaceutical Form: Solution for injection * Route of Administration: intravenous

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Subject is male or female, 18 to 70 years of age, inclusive * Subject has an established diagnosis of epilepsy * Subject has been admitted to the institution's Epilepsy Monitoring Unit (EMU) for seizure characterization or noninvasive presurgical evaluation or such admission is planned within 21 days of Screening

Exclusion criteria

* Subject has previously participated in this study and was treated with study drug. Re-screen is permitted * Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within the previous 30 days of Epilepsy Monitoring Unit (EMU) admission or is currently participating in another study of an IMP or a medical device * Subject has taken brivaracetam (BRV) in the 21 days prior to EMU admission * History or presence of status epilepticus during the 6 months prior to EMU admission * Subject has a medical or psychiatric condition that in the opinion of the Investigator could jeopardize or would compromise the subject's ability to participate in this study * Subject has \> 2x upper limit of normal (ULN) of any of the following: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or \> ULN total bilirubin * Subject has chronic liver disease * Subject has hypersensitivity to BRV or any of its excipients * Subject has a history of alcohol or drug abuse during the 6 months prior to EMU admission * Subject with a history of psychogenic seizures * Subject is a pregnant or lactating female * Subject has a history of a significant Adverse Event (AE) due to a benzodiazepine in the opinion of the Investigator * Subject has respiratory failure (or is at risk for respiratory failure), untreated sleep apnea, or other severe cardiorespiratory disease with New York Heart Association Class III or IV functional status, or requires supplemental oxygen * Subject has acute narrow-angle glaucoma or myasthenia gravis * Subject is receiving benzodiazepine treatment (defined as an average of \>=4 administrations per week) that started less than 28 days prior to EMU admission * Subject has a known allergic reaction or intolerance to benzodiazepines or benzodiazepine excipients

Design outcomes

Primary

Measure	Time frame	Description
Time to Next Seizure (Per Clinical Observation With Electroencephalogram [EEG] Confirmation) or Rescue Medication	During the Treatment Period (Day 1) until Safety Follow-Up Visit (Day 2)	This variable was calculated in hours. The event of next seizure was defined as the first seizure (clinically observed with electroencephalogram \[EEG\] confirmation) with the start date and time within 12 hours after the end of investigational medicinal product (IMP) administration.

Secondary

Measure	Time frame	Description
Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 6 Hours After the End of Study Drug Administration	At 6 hours after the end of study drug administration	This variable was defined as the number of subjects seizure free during 6 hours after the end of study drug administration divided by the number of subjects in the Intent-to-Treat (ITT) set multiplied by 100.
Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 8 Hours After the End of Study Drug Administration	At 8 hours after the end of study drug administration	This variable was defined as the number of subjects seizure free during 8 hours after the end of study drug administration divided by the number of subjects in the ITT set multiplied by 100.
Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 12 Hours After the End of Study Drug Administration	At 12 hours after the end of study drug administration	This variable was defined as the number of subjects seizure free during 12 hours after the end of study drug administration divided by the number of subjects in the ITT set multiplied by 100.
Time to Next Seizure (Per Clinical Observation) or Rescue Medication	During the Treatment Period (Day 1) until Safety Follow-Up Visit (Day 2)	This variable was calculated in hours. The event of next seizure was defined as the first seizure (clinically observed and not necessarily confirmed via electroencephalogram \[EEG\]) with the start date and time within 12 hours after the end of investigational medicinal product (IMP) administration.
Percentage of Subjects Who Receive Rescue Medication During the 8 Hours After the End of Study Drug Administration	During the 8 hours after the end of study drug administration	This variable was defined as the number of subjects who received rescue medication with start date and time within the first 8 hours after the end of study drug administration divided by the number of subjects in the ITT-R set multiplied by 100.
Percentage of Subjects Who Receive Rescue Medication During the 12 Hours After the End of Study Drug Administration	During the 12 hours after the end of study drug administration	This variable was defined as the number of subjects who received rescue medication with start date and time within the first 12 hours after the end of study drug administration divided by the number of subjects in the ITT-R set multiplied by 100.
Percentage of Subjects Who Receive Rescue Medication During the 6 Hours After the End of Study Drug Administration	During the 6 hours after the end of study drug administration	This variable was defined as the number of subjects who received rescue medication with start date and time within the first 6 hours after the end of study drug administration divided by the number of subjects in the Intent-to-Treat as randomized (ITT-R) set multiplied by 100.

Countries

United States

Participant flow

Recruitment details

The study started to enroll patients in February 2017 and concluded in April 2018.

Pre-assignment details

Participant Flow refers to the Intent-to-Treat as Treated (ITT-T) Set.

Participants by arm

Arm	Count
Lorazepam (LZP) Lorazepam bolus was injected based on information from the patient leaflet/package insert. The lorazepam (LZP) dose was determined according to the Investigator's clinical judgment.	16
Brivaracetam (BRV) 100 mg Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period.	15
Brivaracetam (BRV) 200 mg Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period.	15
Total Title	46
Total	92

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	1	0	0
Overall Study	Fall with subsequent nasal fracture	1	0	0

Baseline characteristics

Characteristic	Lorazepam (LZP)	Brivaracetam (BRV) 100 mg	Brivaracetam (BRV) 200 mg	Total Title
Age, Categorical <=18 years	0 Participants	0 Participants	1 Participants	1 Participants
Age, Categorical >=65 years	0 Participants	1 Participants	1 Participants	2 Participants
Age, Categorical Between 18 and 65 years	16 Participants	14 Participants	13 Participants	43 Participants
Age, Continuous	41.10 years STANDARD_DEVIATION 11.18	43.92 years STANDARD_DEVIATION 12.41	41.59 years STANDARD_DEVIATION 15.98	42.18 years STANDARD_DEVIATION 13.06
Race/Ethnicity, Customized Asian	0 Participants	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Black or African American	4 Participants	2 Participants	2 Participants	8 Participants
Race/Ethnicity, Customized White	12 Participants	12 Participants	12 Participants	36 Participants
Sex: Female, Male Female	11 Participants	8 Participants	4 Participants	23 Participants
Sex: Female, Male Male	5 Participants	7 Participants	11 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 15	0 / 15
other Total, other adverse events	4 / 16	6 / 15	3 / 15
serious Total, serious adverse events	1 / 16	0 / 15	0 / 15

Outcome results

Primary

Time to Next Seizure (Per Clinical Observation With Electroencephalogram [EEG] Confirmation) or Rescue Medication

This variable was calculated in hours. The event of next seizure was defined as the first seizure (clinically observed with electroencephalogram \[EEG\] confirmation) with the start date and time within 12 hours after the end of investigational medicinal product (IMP) administration.

Time frame: During the Treatment Period (Day 1) until Safety Follow-Up Visit (Day 2)