A Study to Assess the Efficacy and Safety of Brivaracetam... | NCT03021018

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Brivaracetam (BRV) 100 mg	Experimental	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period	Drug: Brivaracetam
Brivaracetam (BRV) 200 mg	Experimental	Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period	Drug: Brivaracetam
Lorazepam (LZP)	Active Comparator	Lorazepam bolus is to be injected based on information from the patient leaflet/package insert. The rate of injection should not exceed 2.0 mg/min. The LZP dose will be determined according to the Investigator's clinical judgment.	Drug: Lorazepam

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Brivaracetam	Drug	Pharmaceutical Form: Solution for infusion Concentration: 10 mg/ml Route of Administration: intravenous	Brivaracetam (BRV) 100 mg Brivaracetam (BRV) 200 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	During the Treatment Period (Day 1) until Safety Follow-Up Visit (Day 2)

Secondary Outcomes

Measure	Description	Time Frame
Time to Next Seizure (Per Clinical Observation) or Rescue Medication	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.	During the Treatment Period (Day 1) until Safety Follow-Up Visit (Day 2)

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
UCB Cares	UCB (+1 844 599 2273)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ep0087 108		Birmingham	Alabama	35294	United States
Ep0087 117

Label	URL
Product Information	View source
FDA Safety Alerts and Recalls	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Brivaracetam (BRV) 100 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 26, 2017	Apr 23, 2019

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	Brivaracetam (BRV) 100 mg	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period.
BG002	Brivaracetam (BRV) 200 mg	Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period.
BG003	Total Title

Units	Counts
Participants	BG00016 BG00115 BG00215 BG00346

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0021 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00041.10± 11.18 BG00143.92± 12.41 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00011 BG0018 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG0000 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Median

95% Confidence Interval

hours

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

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002	Brivaracetam (BRV) 200 mg (ITT-R)	Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Units	Counts
Participants	OG00015 OG00115 OG00215

Title

Denominators

Categories

Title	Measurements
	OG000NA(5.55 to NA)Due to the low numbers of events seen in the study, the Upper Confidence Limit (UCL) was not calculable. OG001NA(6.93 to NA)Due to the low numbers of events seen in the study, the Upper Confidence Limit (UCL) was not calculable. OG002

Secondary

Time to Next Seizure (Per Clinical Observation) or Rescue Medication

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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Median

95% Confidence Interval

hours

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

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002

Secondary

Percentage of Subjects Who Are Seizure-free Per Clinical Observation 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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Number

percentage of participants

At 6 hours after the end of study drug administration

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002	Brivaracetam (BRV) 200 mg (ITT-R)

Secondary

Percentage of Subjects Who Are Seizure-free Per Clinical Observation 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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Number

percentage of participants

At 8 hours after the end of study drug administration

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002	Brivaracetam (BRV) 200 mg (ITT-R)

Secondary

Percentage of Subjects Who Are Seizure-free Per Clinical Observation 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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Number

percentage of participants

At 12 hours after the end of study drug administration

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002	Brivaracetam (BRV) 200 mg (ITT-R)

Secondary

Percentage of Subjects Who Receive Rescue Medication 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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Number

percentage of participnats

During the 6 hours after the end of study drug administration

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Secondary

Percentage of Subjects Who Receive Rescue Medication 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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Number

percentage of participants

During the 8 hours after the end of study drug administration

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002

Secondary

Percentage of Subjects Who Receive Rescue Medication 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.

The Intent-to-Treat as Randomized (ITT-R) Set consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.

Posted

Number

percentage of participnats

During the 12 hours after the end of study drug administration

ID	Title	Description
OG000	Lorazepam (LZP) (ITT-R)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Randomized (ITT-R) Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG001	Brivaracetam (BRV) 100 mg (ITT-R)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-R Set which consisted of all randomized subjects who received the investigational medicinal product (IMP) for qualifying seizures.
OG002

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lorazepam (LZP) (ITT-T)	Lorazepam bolus was injected based on information from the patient leaflet/package insert. The LZP dose was determined according to the Investigator's clinical judgment. Subjects formed the Intent-to-Treat as Treated (ITT-T) Set which consisted of subjects who were treated with investigational medicinal product (IMP) regardless of qualifying seizure status.	16	1	16	4	16
EG001	Brivaracetam (BRV) 100 mg (ITT-T)	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period. Subjects formed the ITT-T Set which consisted of subjects who were treated with investigational medicinal product (IMP) regardless of qualifying seizure status.	15	0	15	6	15
EG002	Brivaracetam (BRV) 200 mg (ITT-T)	Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period. Subjects formed the ITT-T Set which consisted of subjects who were treated with investigational medicinal product (IMP) regardless of qualifying seizure status.	15	0	15	3	15

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrioventricular dissociation	Cardiac disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected15 at risk
Tachycardia	Cardiac disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected15 at risk
Vertigo	Ear and labyrinth disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected15 at risk
Nausea	Gastrointestinal disorders	MedDRA18.1	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected15 at risk EG0022 events2 affected15 at risk
Vomiting	Gastrointestinal disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0021 events1 affected15 at risk
Vessel puncture site pain	General disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected15 at risk
Fatigue	General disorders	MedDRA18.1	Non-systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected15 at risk
Pain	General disorders	MedDRA18.1	Non-systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected15 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0021 events1 affected15 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected15 at risk
Dizziness	Nervous system disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected15 at risk EG0021 events1 affected15 at risk
Headache	Nervous system disorders	MedDRA18.1	Non-systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected15 at risk EG0020 events0 affected15 at risk
Hypoaesthesia	Nervous system disorders	MedDRA18.1	Non-systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected15 at risk
Sedation	Nervous system disorders	MedDRA18.1	Non-systematic Assessment	EG0002 events2 affected16 at risk EG0010 events0 affected15 at risk EG0021 events1 affected15 at risk
Seizure	Nervous system disorders	MedDRA18.1	Non-systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0021 events1 affected15 at risk
Somnolence	Nervous system disorders	MedDRA18.1	Non-systematic Assessment	EG0002 events2 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected15 at risk

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D001570	Benzodiazepinones
D001569	Benzodiazepines
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds