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

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03021018
• Collaborator: (none)
• Enrollment: 46
• Locations: 14
• Arms: 3
• Actual Duration (Months): 14.6
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Brivaracetam; Drug: Lorazepam	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 6, 2017
• Actual Primary Completion Date: Apr 27, 2018
• Actual Study Completion Date: Apr 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brivaracetam (BRV) 100 mg Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period	Drug: Brivaracetam; Pharmaceutical Form: Solution for infusion Concentration: 10 mg/ml Route of Administration: intravenous; Other Names: Briviact
Experimental: Brivaracetam (BRV) 200 mg Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period	Drug: Brivaracetam; Pharmaceutical Form: Solution for infusion Concentration: 10 mg/ml Route of Administration: intravenous; Other Names: Briviact
Active Comparator: Lorazepam (LZP) 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; Pharmaceutical Form: Solution for injection Route of Administration: intravenous

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ep0087 108	Birmingham	Alabama	United States	35294
2	Ep0087 117	Tucson	Arizona	United States	85724
3	Ep0087 112	Orlando	Florida	United States	32806
4	Ep0087 115	Chicago	Illinois	United States	60611
5	Ep0087 113	Chicago	Illinois	United States	60612
6	Ep0087 119	Wichita	Kansas	United States	67214
7	Ep0087 116	Belmont	Massachusetts	United States	02478
8	Ep0087 106	Boston	Massachusetts	United States	02215
9	Ep0087 107	Detroit	Michigan	United States	48201
10	Ep0087 125	Lebanon	New Hampshire	United States	03756
11	Ep0087 120	Rochester	New York	United States	14642
12	Ep0087 121	Chapel Hill	North Carolina	United States	27599
13	Ep0087 105	Charlotte	North Carolina	United States	28204
14	Ep0087 123	Hershey	Pennsylvania	United States	17033-2360

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares, UCB ([phone])

Study Documents (Full-Text)

• Study Protocol - May 26, 2017
• Statistical Analysis Plan - Mar 23, 2018

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT03021018
• Other Study ID Numbers: EP0087
• First Posted: Jan 13, 2017
• Last Update Posted: Dec 16, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by UCB Biopharma S.P.R.L.: Epilepsy; Brivaracetam; Epilepsy Monitoring Unit; Increased seizure activity
• Additional relevant MeSH terms: Epilepsy; Seizures; Lorazepam; Brivaracetam

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in February 2017 and concluded in April 2018.
Pre-assignment Detail	Participant Flow refers to the Intent-to-Treat as Treated (ITT-T) Set.

Arm/Group Title	Lorazepam (LZP)	Brivaracetam (BRV) 100 mg	Brivaracetam (BRV) 200 mg
Arm/Group Description	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.	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period.	Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period.
Period Title: Overall Study
STARTED	16	15	15
COMPLETED	14	15	15
NOT COMPLETED	2	0	0

Baseline Characteristics

Arm/Group Title	Lorazepam (LZP)	Brivaracetam (BRV) 100 mg	Brivaracetam (BRV) 200 mg	Total Title
Arm/Group Description	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.	Two 5 ml vials of brivaracetam administered intravenously over a 2-minute period.	Four 5 ml vials of brivaracetam administered intravenously over a 4-minute period.
Overall Participants	16	15	15	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	1 6.7%	1 2.2%
Between 18 and 65 years	16 100%	14 93.3%	13 86.7%	43 93.5%
>=65 years	0 0%	1 6.7%	1 6.7%	2 4.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.10 (11.18)	43.92 (12.41)	41.59 (15.98)	42.18 (13.06)
Sex: Female, Male (Count of Participants)
Female	11 68.8%	8 53.3%	4 26.7%	23 50%
Male	5 31.3%	7 46.7%	11 73.3%	23 50%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	1 6.7%	1 6.7%	2 4.3%
Black or African American	4 25%	2 13.3%	2 13.3%	8 17.4%
White	12 75%	12 80%	12 80%	36 78.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Median (95% Confidence Interval) [hours]	NA	NA	NA

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Median (95% Confidence Interval) [hours]	NA	NA	NA

3. Secondary Outcome

Title	Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 6 Hours After the End of Study Drug Administration
Description	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.
Time Frame	At 6 hours after the end of study drug administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Number [percentage of participants]	73.3 458.1%	86.7 578%	80.0 533.3%

4. Secondary Outcome

Title	Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 8 Hours After the End of Study Drug Administration
Description	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.
Time Frame	At 8 hours after the end of study drug administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Number [percentage of participants]	73.3 458.1%	80.0 533.3%	80.0 533.3%

5. Secondary Outcome

Title	Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 12 Hours After the End of Study Drug Administration
Description	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 Frame	At 12 hours after the end of study drug administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Number [percentage of participants]	60.0 375%	80.0 533.3%	80.0 533.3%

6. Secondary Outcome

Title	Percentage of Subjects Who Receive Rescue Medication During the 6 Hours After the End of Study Drug Administration
Description	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.
Time Frame	During the 6 hours after the end of study drug administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Number [percentage of participnats]	20.0	0	6.7

7. Secondary Outcome

Title	Percentage of Subjects Who Receive Rescue Medication During the 8 Hours After the End of Study Drug Administration
Description	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.
Time Frame	During the 8 hours after the end of study drug administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Number [percentage of participants]	26.7 166.9%	6.7 44.7%	13.3 88.7%

8. Secondary Outcome

Title	Percentage of Subjects Who Receive Rescue Medication During the 12 Hours After the End of Study Drug Administration
Description	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.
Time Frame	During the 12 hours after the end of study drug administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lorazepam (LZP) (ITT-R)	Brivaracetam (BRV) 100 mg (ITT-R)	Brivaracetam (BRV) 200 mg (ITT-R)
Arm/Group Description	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.	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.	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.
Measure Participants	15	15	15
Number [percentage of participnats]	40.0	6.7	13.3

Adverse Events

Time Frame	From Screening, at Day -28 and up to Safety Follow-Up (24 hours after the end of drug administration).
Arm/Group Title	Lorazepam (LZP) (ITT-T)		Brivaracetam (BRV) 100 mg (ITT-T)		Brivaracetam (BRV) 200 mg (ITT-T)
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Lorazepam (LZP) (ITT-T)		Brivaracetam (BRV) 100 mg (ITT-T)		Brivaracetam (BRV) 200 mg (ITT-T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Lorazepam (LZP) (ITT-T)		Brivaracetam (BRV) 100 mg (ITT-T)		Brivaracetam (BRV) 200 mg (ITT-T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		0/15 (0%)		0/15 (0%)
Nervous system disorders
Seizure cluster	1/16 (6.3%)	1	0/15 (0%)	0	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	Lorazepam (LZP) (ITT-T)		Brivaracetam (BRV) 100 mg (ITT-T)		Brivaracetam (BRV) 200 mg (ITT-T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/16 (25%)		6/15 (40%)		3/15 (20%)
Cardiac disorders
Atrioventricular dissociation	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Tachycardia	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Ear and labyrinth disorders
Vertigo	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Gastrointestinal disorders
Nausea	0/16 (0%)	0	2/15 (13.3%)	2	2/15 (13.3%)	2
Vomiting	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
General disorders
Vessel puncture site pain	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Fatigue	1/16 (6.3%)	1	0/15 (0%)	0	0/15 (0%)	0
Pain	1/16 (6.3%)	1	0/15 (0%)	0	0/15 (0%)	0
Investigations
Gamma-glutamyltransferase increased	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Dizziness	0/16 (0%)	0	3/15 (20%)	3	1/15 (6.7%)	1
Headache	1/16 (6.3%)	1	2/15 (13.3%)	2	0/15 (0%)	0
Hypoaesthesia	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Sedation	2/16 (12.5%)	2	0/15 (0%)	0	1/15 (6.7%)	1
Seizure	1/16 (6.3%)	1	0/15 (0%)	0	1/15 (6.7%)	1
Somnolence	2/16 (12.5%)	2	0/15 (0%)	0	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.