Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures (BRITE)

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Brivaracetam in Subjects (≥16 to 80 Years Old) With Partial Onset Seizures

This study will evaluate the efficacy and safety of brivaracetam at doses of 100 and 200mg/day compared to placebo as adjunctive treatment in adult focal epilepsy subjects with partial onset seizures not fully controlled despite current treatment with 1 or 2 concomitant antiepileptic drugs.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Placebo; Drug: Antiepileptic drugs with market authorization available per country; Drug: Brivaracetam; Drug: Brivaracetam

• Study Type: Interventional
• Enrollment (Actual): 768
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • 202
  • Linz, Austria
    • 201
  • Wien, Austria
    • 200
  • Wien, Austria
    • 203
• Belgium
  • Hechteleksel, Belgium
    • 226
  • Leuven, Belgium
    • 227
  • Liege, Belgium
    • 228
• Brazil
  • Belo Horizonte, Brazil
    • 104
  • Florianopolis, Brazil
    • 100
  • Riberao Preto, Brazil
    • 103
  • Sao Paulo, Brazil
    • 101
• Bulgaria
  • Blagoevrad, Bulgaria
    • 294
  • Sofiya, Bulgaria
    • 286
  • Sofiya, Bulgaria
    • 287
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • 075
  • Ontario
    • London, Ontario, Canada
      • 078
    • Toronto, Ontario, Canada
      • 076
  • Quebec
    • Greenfield Park, Quebec, Canada
      • 077
    • Montreal, Quebec, Canada
      • 079
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 080
• Czechia
  • Kromeriz, Czechia
    • 916
  • Ostrava, Czechia
    • 251
  • Ostrava, Czechia
    • 256
  • Ostrava Poruba, Czechia
    • 913
  • Praha 1, Czechia
    • 252
  • Praha 4, Czechia
    • 253
  • Zlin, Czechia
    • 250
• Estonia
  • Tallinn, Estonia
    • 650
  • Tallinn, Estonia
    • 652
  • Tallinn, Estonia
    • 653
  • Tartu, Estonia
    • 651
• Finland
  • Kuopio, Finland
    • 275
  • Oulu, Finland
    • 278
  • Tampere, Finland
    • 276
  • Turku, Finland
    • 277
• France
  • Bethune, France
    • 301
  • Marseille, France
    • 308
  • Montpellier, France
    • 305
• Germany
  • Berlin, Germany
    • 329
  • Bernau, Germany
    • 326
  • Bielefeld, Germany
    • 332
  • Erlangen, Germany
    • 902
  • Goettingen, Germany
    • 331
  • Kehl-Kork, Germany
    • 904
  • Kiel, Germany
    • 327
  • Marburg, Germany
    • 900
  • Muenchen, Germany
    • 335
  • Osnabruck, Germany
    • 334
  • Ravensburg, Germany
    • 330
  • Ulm, Germany
    • 328
• Hong Kong
  • Hong Kong, Hong Kong
    • 701
  • Shatin, Hong Kong
    • 700
• Hungary
  • Budapest, Hungary
    • 410
  • Budapest, Hungary
    • 411
  • Budapest, Hungary
    • 412
  • Debrecen, Hungary
    • 414
  • Kecskemet, Hungary
    • 413
• India
  • Bangalore, India
    • 726
  • Madurai, India
    • 729
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India
      • 727
  • Maharashtra
    • Nashik, Maharashtra, India
      • 731
  • Maharastra
    • Mumbai, Maharastra, India
      • 725
    • Mumbai, Maharastra, India
      • 728
• Italy
  • Bari, Italy
    • 378
  • Firenze, Italy
    • 380
  • Milano, Italy
    • 379
  • Napoli, Italy
    • 386
  • Perugia, Italy
    • 376
  • Pisa, Italy
    • 375
  • Pozzilli, Italy
    • 383
  • Reggio Calabria, Italy
    • 384
  • Torino, Italy
    • 382
  • Cagliari
    • Monserrato, Cagliari, Italy
      • 377
• Japan
  • Hiroshima, Japan
    • 855
  • Itami-city, Japan
    • 852
  • Osaka, Japan
    • 850
  • Shizuoka, Japan
    • 851
  • Yokohama-City, Japan
    • 854
• Korea, Republic of
  • Busan, Korea, Republic of
    • 753
  • Gwangju, Korea, Republic of
    • 752
  • Seoul, Korea, Republic of
    • 750
  • Seoul, Korea, Republic of
    • 751
  • Seoul, Korea, Republic of
    • 754
• Latvia
  • Daugapils, Latvia
    • 627
  • Jekabpils, Latvia
    • 629
  • Riga, Latvia
    • 626
  • Riga, Latvia
    • 628
  • Valmiera, Latvia
    • 625
• Lithuania
  • Alytus, Lithuania
    • 425
  • Kaunas, Lithuania
    • 427
  • Vilnius, Lithuania
    • 426
• Mexico
  • Aguascalientes, Mexico
    • 129
  • Culiacan, Mexico
    • 127
  • Distrito Federal, Mexico
    • 125
  • Mexico D.F., Mexico
    • 130
  • Jalisco
    • Guadalajara, Jalisco, Mexico
      • 126
    • Guadalajara, Jalisco, Mexico
      • 128
• Netherlands
  • Heemstede, Netherlands
    • 401
  • Heeze, Netherlands
    • 400
  • Zwolle, Netherlands
    • 403
• Poland
  • Bialystok, Poland
    • 475
  • Gdansk, Poland
    • 485
  • Gdansk, Poland
    • 791
  • Katowice, Poland
    • 478
  • Katowice, Poland
    • 480
  • Katowice, Poland
    • 481
  • Krakow, Poland
    • 476
  • Krakow, Poland
    • 793
  • Lublin, Poland
    • 483
  • Poznan, Poland
    • 479
  • Poznan, Poland
    • 477
  • Poznan, Poland
    • 482
  • Warszawa, Poland
    • 488
• Puerto Rico
  • San Juan, Puerto Rico
    • 038
• Russian Federation
  • Kazan, Russian Federation
    • 501
  • Kazan, Russian Federation
    • 506
  • Moscow, Russian Federation
    • 502
  • Moscow, Russian Federation
    • 503
  • Moscow, Russian Federation
    • 505
  • Nizhny Novgorod, Russian Federation
    • 509
  • Smolensk, Russian Federation
    • 508
• Spain
  • Badalona, Spain
    • 536
  • Barcelona, Spain
    • 528
  • Barcelona, Spain
    • 529
  • Barcelona, Spain
    • 535
  • Barcelona, Spain
    • 540
  • San Sebastian, Spain
    • 539
  • Santiago de Compostela, Spain
    • 532
  • Valencia, Spain
    • 527
  • Valencia, Spain
    • 537
  • Valladolid, Spain
    • 526
• Sweden
  • Goteborg, Sweden
    • 551
  • Linkoping, Sweden
    • 552
  • Stockholm, Sweden
    • 550
• Taiwan
  • Kaohsiung City, Taiwan
    • 806
  • Taichung, Taiwan
    • 801
  • Tainan, Taiwan
    • 800
  • Taoyuan Hsien, Taiwan
    • 803
• United Kingdom
  • Birmingham, United Kingdom
    • 603
  • Cardiff, United Kingdom
    • 606
  • Cornwall, United Kingdom
    • 601
  • London, United Kingdom
    • 600
  • Middlesborough, United Kingdom
    • 605
  • Newcastle, United Kingdom
    • 607
  • Salford, United Kingdom
    • 608
  • Swansea, United Kingdom
    • 602
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • 001
    • Phoenix, Arizona, United States
      • 013
    • Tucson, Arizona, United States
      • 006
  • Arkansas
    • Little Rock, Arkansas, United States
      • 775
  • California
    • Sacramento, California, United States
      • 045
    • San Francisco, California, United States
      • 025
  • Colorado
    • Aurora, Colorado, United States
      • 060
    • Colorado Springs, Colorado, United States
      • 085
  • Florida
    • Miami, Florida, United States
      • 071
    • Miami, Florida, United States
      • 110
    • Naples, Florida, United States
      • 073
    • Ocala, Florida, United States
      • 090
    • Orlando, Florida, United States
      • 027
    • Port Charlotte, Florida, United States
      • 064
    • Sarasota, Florida, United States
      • 044
  • Georgia
    • Atlanta, Georgia, United States
      • 023
    • Atlanta, Georgia, United States
      • 063
    • Columbus, Georgia, United States
      • 062
    • Rome, Georgia, United States
      • 048
  • Idaho
    • Boise, Idaho, United States
      • 039
  • Illinois
    • Peoria, Illinois, United States
      • 005
    • Winfield, Illinois, United States
      • 017
  • Iowa
    • Ames, Iowa, United States
      • 020
    • Iowa City, Iowa, United States
      • 069
  • Kentucky
    • Lexington, Kentucky, United States
      • 780
  • Louisiana
    • Hammond, Louisiana, United States
      • 092
  • Maryland
    • Bethesda, Maryland, United States
      • 008
    • Waldorf, Maryland, United States
      • 068
  • Michigan
    • East Lansing, Michigan, United States
      • 055
  • Minnesota
    • Golden Valley, Minnesota, United States
      • 009
  • Montana
    • Missoula, Montana, United States
      • 051
  • New Hampshire
    • Lebanon, New Hampshire, United States
      • 032
  • New Jersey
    • Hamilton, New Jersey, United States
      • 042
    • Voorhees, New Jersey, United States
      • 058
  • New York
    • Kingston, New York, United States
      • 095
    • New York, New York, United States
      • 022
    • New York, New York, United States
      • 099
    • Poughkeepsie, New York, United States
      • 098
  • North Carolina
    • Asheville, North Carolina, United States
      • 010
    • Durham, North Carolina, United States
      • 003
  • Ohio
    • Canton, Ohio, United States
      • 096
    • Cleveland, Ohio, United States
      • 034
    • Columbus, Ohio, United States
      • 070
    • Toledo, Ohio, United States
      • 002
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • 043
    • Oklahoma City, Oklahoma, United States
      • 091
    • Tulsa, Oklahoma, United States
      • 054
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 015
  • South Carolina
    • Charleston, South Carolina, United States
      • 028
    • Port Royal, South Carolina, United States
      • 021
  • Texas
    • Arlington, Texas, United States
      • 050
    • Austin, Texas, United States
      • 061
    • Dallas, Texas, United States
      • 011
    • Dallas, Texas, United States
      • 035
    • Houston, Texas, United States
      • 049
  • Virginia
    • Charlottesville, Virginia, United States
      • 036
  • Washington
    • Seattle, Washington, United States
      • 033
    • Spokane, Washington, United States
      • 056
  • Wisconsin
    • Madison, Wisconsin, United States
      • 052
    • Milwaukee, Wisconsin, United States
      • 057
  • Wyoming
    • Casper, Wyoming, United States
      • 089

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 78 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Well-characterized focal epilepsy/epileptic syndrome according to the 1989 International League Against Epilepsy (ILAE) classification
• Presence of an EEG reading compatible with the clinical diagnosis of focal epilepsy within the last 5 years
• Presence of a brain MRI/computed tomography (CT) scan performed within the last 2 years
• Subjects having at least 8 Type I seizures [POS; focal seizures (according to the 1981 ILAE classification)] during the 8-week Baseline Period with at least 2 Type I seizures during each 4-week interval of the Baseline Period
• Subjects having at least 2 partial onset seizures whether or not secondarily generalized per month during the 3 months preceding V1
• Subjects being uncontrolled while treated by 1 or 2 permitted concomitant AED(s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
• Permitted concomitant AED(s) and VNS being stable and at optimal dosage for the subject from at least 1 month (3 months for phenobarbital, phenytoin, and primidone) before V1 and expected to be kept stable during the Baseline and Treatment Period. Benzodiazepine taken more than once a week (for any indication) will be considered as a concomitant AED

Exclusion Criteria:

• Subject previously randomized within this study or any other prior study with BRV as a dosing arm
• Seizure type IA (1981 ILAE classification) nonmotor as only seizure type.
• Subject is currently treated with LEV or has taken LEV within 90 days prior to V1
• Subject has any medical or psychiatric condition, obvious cognitive impairment or mental retardation that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study
• Subjects whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries)
• Subject has history or presence of status epilepticus during the year preceding V1 or during Baseline
• Subject has history or presence of known psychogenic nonepileptic seizures
• Subject on felbamate with less than 18 months exposure before V1
• Subject currently on vigabatrin. Subject with history of vigabatrin use but either no visual fields examination report available including standard static (Humphrey or Octopus) or kinetic perimetry (Goldman) or results of these examinations are abnormal
• Subject taking any drug with possible central nervous system (CNS) effects except if stable from at least 1 month before V1 and expected to be kept stable during the Treatment Period
• Subject has history of cerebrovascular accident, including transient ischemic attack, in the last 6 months
• Subject is suffering from severe cardiovascular disease or peripheral vascular disease
• Subject has a lifetime history of suicide attempt or has suicidal ideation in the past 6 months
• Subject has ongoing psychiatric disease other than mild controlled disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo tablets administered twice daily	Drug: Placebo; Daily oral dose of two equal intakes of placebo in a double-blinded way for the 12-week treatment period; Drug: Antiepileptic drugs with market authorization available per country
Experimental: Brivaracetam 100 mg/ day; Brivaracetam 50 mg/ day administered twice daily.	Drug: Antiepileptic drugs with market authorization available per country; Drug: Brivaracetam; Daily oral dose of two equal intakes of Brivaracetam 100 mg/ day in a double-blinded way for the 12-week treatment period; Drug: Brivaracetam; Daily oral dose of two equal intakes of Brivaracetam 200 mg/ day in a double-blinded way for the 12-week treatment period.
Experimental: Brivaracetam 200 mg/ day; Brivaracetam 100 mg/ day administered twice daily	Drug: Antiepileptic drugs with market authorization available per country; Drug: Brivaracetam; Daily oral dose of two equal intakes of Brivaracetam 100 mg/ day in a double-blinded way for the 12-week treatment period; Drug: Brivaracetam; Daily oral dose of two equal intakes of Brivaracetam 200 mg/ day in a double-blinded way for the 12-week treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Reduction Over Placebo for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration	Primary endpoint: United States of America (FDA)	12 week Treatment Period
50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration	Primary Endpoint: European Regulatory Authorities A responder is a participant who experienced a 50% or greater reduction in partial onset seizure (Type I) frequency over the Treatment Period standardized to a 28-day duration.	Baseline to 12 week Treatment Period

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change in Partial Onset Seizure (Type I) Frequency From the Baseline to the Treatment Period	Baseline to 12 week Treatment Period
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period	Baseline to 12 week Treatment Period
Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period	12 week Treatment Period
All Seizure Frequency (Type I + II + III) During the 12-week Treatment Period	12 week Treatment Period
Time to the First Type I Seizure During the Treatment Period	12 week Treatment Period
Time to the Fifth Type I Seizure During the Treatment Period	12 week Treatment Period
Time to the Tenth Type I Seizure During the Treatment Period	12 week Treatment Period

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• Toledo M, Brandt C, Quarato PP, Schulz AL, Cleveland JM, Wagener G, Klein P. Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial. Epilepsy Behav. 2021 May;118:107897. doi: 10.1016/j.yebeh.2021.107897. Epub 2021 Mar 27.
• Markham A. Brivaracetam: First Global Approval. Drugs. 2016 Mar;76(4):517-22. doi: 10.1007/s40265-016-0555-6.
• Toledo M, Whitesides J, Schiemann J, Johnson ME, Eckhardt K, McDonough B, Borghs S, Kwan P. Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures. Epilepsia. 2016 Jul;57(7):1139-51. doi: 10.1111/epi.13416. Epub 2016 Jun 6.
• Ben-Menachem E, Mameniskiene R, Quarato PP, Klein P, Gamage J, Schiemann J, Johnson ME, Whitesides J, McDonough B, Eckhardt K. Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies. Neurology. 2016 Jul 19;87(3):314-23. doi: 10.1212/WNL.0000000000002864. Epub 2016 Jun 22.
• Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, Brandt C, Kwan P. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015 Dec;56(12):1890-8. doi: 10.1111/epi.13212. Epub 2015 Oct 16.
• Brodie MJ, Whitesides J, Schiemann J, D'Souza J, Johnson ME. Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies. Epilepsy Res. 2016 Nov;127:114-118. doi: 10.1016/j.eplepsyres.2016.08.018. Epub 2016 Aug 18.
• Moseley BD, Sperling MR, Asadi-Pooya AA, Diaz A, Elmouft S, Schiemann J, Whitesides J. Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies. Epilepsy Res. 2016 Nov;127:179-185. doi: 10.1016/j.eplepsyres.2016.09.003. Epub 2016 Sep 3.
• Brandt C, Borghs S, Elmoufti S, Mueller K, Townsend R, de la Loge C. Health-related quality of life in double-blind Phase III studies of brivaracetam as adjunctive therapy of focal seizures: A pooled, post-hoc analysis. Epilepsy Behav. 2017 Apr;69:80-85. doi: 10.1016/j.yebeh.2016.11.031. Epub 2017 Feb 23.
• Klein P, Johnson ME, Schiemann J, Whitesides J. Time to onset of sustained >/=50% responder status in patients with focal (partial-onset) seizures in three phase III studies of adjunctive brivaracetam treatment. Epilepsia. 2017 Feb;58(2):e21-e25. doi: 10.1111/epi.13631. Epub 2016 Dec 18.
• Asadi-Pooya AA, Sperling MR, Chung S, Klein P, Diaz A, Elmoufti S, Schiemann J, Whitesides J. Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study. Epilepsy Res. 2017 Mar;131:70-75. doi: 10.1016/j.eplepsyres.2017.02.007. Epub 2017 Feb 27. Erratum In: Epilepsy Res. 2017 Nov;137:165-166.
• Benbadis S, Klein P, Schiemann J, Diaz A, Elmoufti S, Whitesides J. Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A post-hoc analysis. Epilepsy Behav. 2018 Mar;80:129-134. doi: 10.1016/j.yebeh.2017.12.024. Epub 2018 Feb 3.
• Brodie MJ, Fakhoury T, McDonough B, Colson AO, Stockis A, Elmoufti S, Whitesides J. Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. Epilepsy Res. 2018 Sep;145:55-62. doi: 10.1016/j.eplepsyres.2018.06.002. Epub 2018 Jun 4.
• Klein P, Laloyaux C, Elmoufti S, Gasalla T, Martin MS. Time course of 75%-100% efficacy response of adjunctive brivaracetam. Acta Neurol Scand. 2020 Aug;142(2):175-180. doi: 10.1111/ane.13287. Epub 2020 Jun 9.
• Moseley BD, Dimova S, Elmoufti S, Laloyaux C, Asadi-Pooya AA. Long-term efficacy and tolerability of adjunctive brivaracetam in adults with focal to bilateral tonic-clonic (secondary generalized) seizures: Post hoc pooled analysis. Epilepsy Res. 2021 Oct;176:106694. doi: 10.1016/j.eplepsyres.2021.106694. Epub 2021 Jun 24.
• Ryvlin P, Dimova S, Elmoufti S, Floricel F, Laloyaux C, Nondonfaz X, Biton V. Tolerability and efficacy of adjunctive brivaracetam in adults with focal seizures by concomitant antiseizure medication use: Pooled results from three phase 3 trials. Epilepsia. 2022 Aug;63(8):2024-2036. doi: 10.1111/epi.17304. Epub 2022 Jun 10.
• Bresnahan R, Panebianco M, Marson AG. Brivaracetam add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2022 Mar 14;3:CD011501. doi: 10.1002/14651858.CD011501.pub3. Review.
• Lee SK, Heo K, Kim SE, Lee SA, Elmoufti S, Laloyaux C, Hur B. Effect of Number of Previous Antiseizure Medications on Efficacy and Tolerability of Adjunctive Brivaracetam for Uncontrolled Focal Seizures: Post Hoc Analysis. Adv Ther. 2021 Jul;38(7):4082-4099. doi: 10.1007/s12325-021-01816-5. Epub 2021 Jun 21.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 9, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimate): December 16, 2010

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Epilepsy; Brivaracetam; Partial Onset Seizures; Adjunctive treatment
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Anticonvulsants; Brivaracetam
• Other Study ID Numbers: N01358; 2010-019361-28 (EudraCT Number)