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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Brivaracetam; Drug: Lorazepam

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Ep0087 108
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Ep0087 117
  • Florida
    • Orlando, Florida, United States, 32806
      • Ep0087 112
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ep0087 115
    • Chicago, Illinois, United States, 60612
      • Ep0087 113
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Ep0087 119
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Ep0087 116
    • Boston, Massachusetts, United States, 02215
      • Ep0087 106
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Ep0087 107
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Ep0087 125
  • New York
    • Rochester, New York, United States, 14642
      • Ep0087 120
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Ep0087 121
    • Charlotte, North Carolina, United States, 28204
      • Ep0087 105
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-2360
      • Ep0087 123

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2017
• Primary Completion (Actual): April 27, 2018
• Study Completion (Actual): April 27, 2018

Study Registration Dates

• First Submitted: January 11, 2017
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimate): January 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Epilepsy; Brivaracetam; Epilepsy Monitoring Unit; Increased seizure activity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Lorazepam; Brivaracetam
• Other Study ID Numbers: EP0087

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.clinicalstudydatarequest.com and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if a determination is made that the data cannot be adequately anonymized.
• IPD Sharing Time Frame: Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.clinicalstudydatarequest.com and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No