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

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ClinicalTrials.gov Identifier: NCT03021018
Recruitment Status : Completed
First Posted : January 13, 2017
Results First Posted : May 27, 2019
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Interventions Drug: Brivaracetam
Drug: Lorazepam
Enrollment 46
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.
Arm/Group Title Lorazepam (LZP) Brivaracetam (BRV) 100 mg Brivaracetam (BRV) 200 mg
Hide 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
Reason Not Completed
Adverse Event             1             0             0
Fall with subsequent nasal fracture             1             0             0
Arm/Group Title Lorazepam (LZP) Brivaracetam (BRV) 100 mg Brivaracetam (BRV) 200 mg Total Title
Hide 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. [Not Specified]
Overall Number of Baseline Participants 16 15 15 46
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Intent-to-Treat as Treated Set which consisted of subjects who were treated with investigational medicinal product (IMP) regardless of qualifying seizure status.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 15 participants 46 participants
<=18 years
0
   0.0%
0
   0.0%
1
   6.7%
1
   2.2%
Between 18 and 65 years
16
 100.0%
14
  93.3%
13
  86.7%
43
  93.5%
>=65 years
0
   0.0%
1
   6.7%
1
   6.7%
2
   4.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 15 participants 15 participants 46 participants
41.10  (11.18) 43.92  (12.41) 41.59  (15.98) 42.18  (13.06)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 15 participants 46 participants
Female
11
  68.8%
8
  53.3%
4
  26.7%
23
  50.0%
Male
5
  31.3%
7
  46.7%
11
  73.3%
23
  50.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 15 participants 46 participants
Asian
0
   0.0%
1
   6.7%
1
   6.7%
2
   4.3%
Black or African American
4
  25.0%
2
  13.3%
2
  13.3%
8
  17.4%
White
12
  75.0%
12
  80.0%
12
  80.0%
36
  78.3%
1.Primary Outcome
Title Time to Next Seizure (Per Clinical Observation With Electroencephalogram [EEG] Confirmation) or Rescue Medication
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Median (95% Confidence Interval)
Unit of Measure: hours
NA [1] 
(5.55 to NA)
NA [1] 
(6.93 to NA)
NA [1] 
(4.33 to NA)
[1]
Due to the low numbers of events seen in the study, the Upper Confidence Limit (UCL) was not calculable.
2.Secondary Outcome
Title Time to Next Seizure (Per Clinical Observation) or Rescue Medication
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Median (95% Confidence Interval)
Unit of Measure: hours
NA [1] 
(5.55 to NA)
NA [1] 
(6.93 to NA)
NA [1] 
(4.33 to NA)
[1]
Due to the low numbers of events seen in the study, the Upper Confidence Limit (UCL) was not calculable.
3.Secondary Outcome
Title Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 6 Hours After the End of Study Drug Administration
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Measure Type: Number
Unit of Measure: percentage of participants
73.3 86.7 80.0
4.Secondary Outcome
Title Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 8 Hours After the End of Study Drug Administration
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Measure Type: Number
Unit of Measure: percentage of participants
73.3 80.0 80.0
5.Secondary Outcome
Title Percentage of Subjects Who Are Seizure-free Per Clinical Observation at 12 Hours After the End of Study Drug Administration
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Measure Type: Number
Unit of Measure: percentage of participants
60.0 80.0 80.0
6.Secondary Outcome
Title Percentage of Subjects Who Receive Rescue Medication During the 6 Hours After the End of Study Drug Administration
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Measure Type: Number
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Measure Type: Number
Unit of Measure: percentage of participants
26.7 6.7 13.3
8.Secondary Outcome
Title Percentage of Subjects Who Receive Rescue Medication During the 12 Hours After the End of Study Drug Administration
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 15 15 15
Measure Type: Number
Unit of Measure: percentage of participnats
40.0 6.7 13.3
Time Frame From Screening, at Day -28 and up to Safety Follow-Up (24 hours after the end of drug administration).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lorazepam (LZP) (ITT-T) Brivaracetam (BRV) 100 mg (ITT-T) Brivaracetam (BRV) 200 mg (ITT-T)
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)      0/15 (0.00%)      0/15 (0.00%)    
Show Serious Adverse Events Hide 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 (6.25%)      0/15 (0.00%)      0/15 (0.00%)    
Nervous system disorders       
Seizure cluster * 1  1/16 (6.25%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
1
Term from vocabulary, MedDRA18.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (25.00%)      6/15 (40.00%)      3/15 (20.00%)    
Cardiac disorders       
Atrioventricular dissociation * 1  0/16 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Tachycardia * 1  0/16 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Ear and labyrinth disorders       
Vertigo * 1  0/16 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Gastrointestinal disorders       
Nausea  1  0/16 (0.00%)  0 2/15 (13.33%)  2 2/15 (13.33%)  2
Vomiting * 1  0/16 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
General disorders       
Vessel puncture site pain * 1  0/16 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Fatigue * 1  1/16 (6.25%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Pain * 1  1/16 (6.25%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Investigations       
Gamma-glutamyltransferase increased * 1  0/16 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain * 1  0/16 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Nervous system disorders       
Dizziness * 1  0/16 (0.00%)  0 3/15 (20.00%)  3 1/15 (6.67%)  1
Headache * 1  1/16 (6.25%)  1 2/15 (13.33%)  2 0/15 (0.00%)  0
Hypoaesthesia * 1  0/16 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Sedation * 1  2/16 (12.50%)  2 0/15 (0.00%)  0 1/15 (6.67%)  1
Seizure * 1  1/16 (6.25%)  1 0/15 (0.00%)  0 1/15 (6.67%)  1
Somnolence * 1  2/16 (12.50%)  2 0/15 (0.00%)  0 0/15 (0.00%)  0
1
Term from vocabulary, MedDRA18.1
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
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
Organization: Cares
Phone: +1844 599 ext 2273
Responsible Party: UCB Pharma ( UCB Biopharma S.P.R.L. )
ClinicalTrials.gov Identifier: NCT03021018     History of Changes
Other Study ID Numbers: EP0087
First Submitted: January 11, 2017
First Posted: January 13, 2017
Results First Submitted: April 26, 2019
Results First Posted: May 27, 2019
Last Update Posted: June 26, 2019