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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Brivaracetam
* Drug: Lorazepam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 Outcome Measures

| Outcome Measure | 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) | 
| 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. | At 6 hours after the end of study drug administration | 
| 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. | At 8 hours after the end of study drug administration | 
| 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. | At 12 hours after the end of study drug administration | 
| 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. | During the 6 hours after the end of study drug administration | 
| 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. | During the 8 hours after the end of study drug administration | 
| 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. | During the 12 hours after the end of study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Brivaracetam, Epilepsy Monitoring Unit, Increased seizure activity