Clinical trial NCT01261325: Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Epilepsy
Brivaracetam
Partial Onset Seizures
Adjunctive treatment
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2010-12-16
Enrollment: 768
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Reduction Over Placebo for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration
timeFrame: 12 week Treatment Period
measure: 50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration
timeFrame: Baseline to 12 week Treatment Period
Secondary outcomes:
measure: Percent Change in Partial Onset Seizure (Type I) Frequency From the Baseline to the Treatment Period
timeFrame: Baseline to 12 week Treatment Period
measure: Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period
timeFrame: Baseline to 12 week Treatment Period
measure: Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period
timeFrame: 12 week Treatment Period
measure: All Seizure Frequency (Type I + II + III) During the 12-week Treatment Period
timeFrame: 12 week Treatment Period
measure: Time to the First Type I Seizure During the Treatment Period
timeFrame: 12 week Treatment Period
measure: Time to the Fifth Type I Seizure During the Treatment Period
timeFrame: 12 week Treatment Period
measure: Time to the Tenth Type I Seizure During the Treatment Period
timeFrame: 12 week Treatment Period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 001
state: Arizona
city: Phoenix
country: United States
facility: 013
state: Arizona
city: Tucson
country: United States
facility: 006
state: Arizona
city: Little Rock
country: United States
facility: 775
state: Arkansas
city: Sacramento
country: United States
facility: 045
state: California
city: San Francisco
country: United States
facility: 025
state: California
city: Aurora
country: United States
facility: 060
state: Colorado
city: Colorado Springs
country: United States
facility: 085
state: Colorado
city: Miami
country: United States
facility: 071
state: Florida
city: Miami
country: United States
facility: 110
state: Florida
city: Naples
country: United States
facility: 073
state: Florida
city: Ocala
country: United States
facility: 090
state: Florida
city: Orlando
country: United States
facility: 027
state: Florida
city: Port Charlotte
country: United States
facility: 064
state: Florida
city: Sarasota
country: United States
facility: 044
state: Florida
city: Atlanta
country: United States
facility: 023
state: Georgia
city: Atlanta
country: United States
facility: 063
state: Georgia
city: Columbus
country: United States
facility: 062
state: Georgia
city: Rome
country: United States
facility: 048
state: Georgia
city: Boise
country: United States
facility: 039
state: Idaho
city: Peoria
country: United States
facility: 005
state: Illinois
city: Winfield
country: United States
facility: 017
state: Illinois
city: Ames
country: United States
facility: 020
state: Iowa
city: Iowa City
country: United States
facility: 069
state: Iowa
city: Lexington
country: United States
facility: 780
state: Kentucky
city: Hammond
country: United States
facility: 092
state: Louisiana
city: Bethesda
country: United States
facility: 008
state: Maryland
city: Waldorf
country: United States
facility: 068
state: Maryland
city: East Lansing
country: United States
facility: 055
state: Michigan
city: Golden Valley
country: United States
facility: 009
state: Minnesota
city: Missoula
country: United States
facility: 051
state: Montana
city: Lebanon
country: United States
facility: 032
state: New Hampshire
city: Hamilton
country: United States
facility: 042
state: New Jersey
city: Voorhees
country: United States
facility: 058
state: New Jersey
city: Kingston
country: United States
facility: 095
state: New York
city: New York
country: United States
facility: 022
state: New York
city: New York
country: United States
facility: 099
state: New York
city: Poughkeepsie
country: United States
facility: 098
state: New York
city: Asheville
country: United States
facility: 010
state: North Carolina
city: Durham
country: United States
facility: 003
state: North Carolina
city: Canton
country: United States
facility: 096
state: Ohio
city: Cleveland
country: United States
facility: 034
state: Ohio
city: Columbus
country: United States
facility: 070
state: Ohio
city: Toledo
country: United States
facility: 002
state: Ohio
city: Oklahoma City
country: United States
facility: 043
state: Oklahoma
city: Oklahoma City
country: United States
facility: 091
state: Oklahoma
city: Tulsa
country: United States
facility: 054
state: Oklahoma
city: Philadelphia
country: United States
facility: 015
state: Pennsylvania
city: Charleston
country: United States
facility: 028
state: South Carolina
city: Port Royal
country: United States
facility: 021
state: South Carolina
city: Arlington
country: United States
facility: 050
state: Texas
city: Austin
country: United States
facility: 061
state: Texas
city: Dallas
country: United States
facility: 011
state: Texas
city: Dallas
country: United States
facility: 035
state: Texas
city: Houston
country: United States
facility: 049
state: Texas
city: Charlottesville
country: United States
facility: 036
state: Virginia
city: Seattle
country: United States
facility: 033
state: Washington
city: Spokane
country: United States
facility: 056
state: Washington
city: Madison
country: United States
facility: 052
state: Wisconsin
city: Milwaukee
country: United States
facility: 057
state: Wisconsin
city: Casper
country: United States
facility: 089
state: Wyoming
city: Innsbruck
country: Austria
facility: 202
city: Linz
country: Austria
facility: 201
city: Wien
country: Austria
facility: 200
city: Wien
country: Austria
facility: 203
city: Hechteleksel
country: Belgium
facility: 226
city: Leuven
country: Belgium
facility: 227
city: Liege
country: Belgium
facility: 228
city: Belo Horizonte
country: Brazil
facility: 104
city: Florianopolis
country: Brazil
facility: 100
city: Riberao Preto
country: Brazil
facility: 103
city: Sao Paulo
country: Brazil
facility: 101
city: Blagoevrad
country: Bulgaria
facility: 294
city: Sofiya
country: Bulgaria
facility: 286
city: Sofiya
country: Bulgaria
facility: 287
city: Calgary
country: Canada
facility: 075
state: Alberta
city: London
country: Canada
facility: 078
state: Ontario
city: Toronto
country: Canada
facility: 076
state: Ontario
city: Greenfield Park
country: Canada
facility: 077
state: Quebec
city: Montreal
country: Canada
facility: 079
state: Quebec
city: Saskatoon
country: Canada
facility: 080
state: Saskatchewan
city: Kromeriz
country: Czechia
facility: 916
city: Ostrava Poruba
country: Czechia
facility: 913
city: Ostrava
country: Czechia
facility: 251
city: Ostrava
country: Czechia
facility: 256
city: Praha 1
country: Czechia
facility: 252
city: Praha 4
country: Czechia
facility: 253
city: Zlin
country: Czechia
facility: 250
city: Tallinn
country: Estonia
facility: 650
city: Tallinn
country: Estonia
facility: 652
city: Tallinn
country: Estonia
facility: 653
city: Tartu
country: Estonia
facility: 651
city: Kuopio
country: Finland
facility: 275
city: Oulu
country: Finland
facility: 278
city: Tampere
country: Finland
facility: 276
city: Turku
country: Finland
facility: 277
city: Bethune
country: France
facility: 301
city: Marseille
country: France
facility: 308
city: Montpellier
country: France
facility: 305
city: Berlin
country: Germany
facility: 329
city: Bernau
country: Germany
facility: 326
city: Bielefeld
country: Germany
facility: 332
city: Erlangen
country: Germany
facility: 902
city: Goettingen
country: Germany
facility: 331
city: Kehl-Kork
country: Germany
facility: 904
city: Kiel
country: Germany
facility: 327
city: Marburg
country: Germany
facility: 900
city: Muenchen
country: Germany
facility: 335
city: Osnabruck
country: Germany
facility: 334
city: Ravensburg
country: Germany
facility: 330
city: Ulm
country: Germany
facility: 328
city: Hong Kong
country: Hong Kong
facility: 701
city: Shatin
country: Hong Kong
facility: 700
city: Budapest
country: Hungary
facility: 410
city: Budapest
country: Hungary
facility: 411
city: Budapest
country: Hungary
facility: 412
city: Debrecen
country: Hungary
facility: 414
city: Kecskemet
country: Hungary
facility: 413
city: Hyderabad
country: India
facility: 727
state: Andhra Pradesh
city: Nashik
country: India
facility: 731
state: Maharashtra
city: Mumbai
country: India
facility: 725
state: Maharastra
city: Mumbai
country: India
facility: 728
state: Maharastra
city: Bangalore
country: India
facility: 726
city: Madurai
country: India
facility: 729
city: Monserrato
country: Italy
facility: 377
state: Cagliari
city: Bari
country: Italy
facility: 378
city: Firenze
country: Italy
facility: 380
city: Milano
country: Italy
facility: 379
city: Napoli
country: Italy
facility: 386
city: Perugia
country: Italy
facility: 376
city: Pisa
country: Italy
facility: 375
city: Pozzilli
country: Italy
facility: 383
city: Reggio Calabria
country: Italy
facility: 384
city: Torino
country: Italy
facility: 382
city: Hiroshima
country: Japan
facility: 855
city: Itami-city
country: Japan
facility: 852
city: Osaka
country: Japan
facility: 850
city: Shizuoka
country: Japan
facility: 851
city: Yokohama-City
country: Japan
facility: 854
city: Busan
country: Korea, Republic of
facility: 753
city: Gwangju
country: Korea, Republic of
facility: 752
city: Seoul
country: Korea, Republic of
facility: 750
city: Seoul
country: Korea, Republic of
facility: 751
city: Seoul
country: Korea, Republic of
facility: 754
city: Daugapils
country: Latvia
facility: 627
city: Jekabpils
country: Latvia
facility: 629
city: Riga
country: Latvia
facility: 626
city: Riga
country: Latvia
facility: 628
city: Valmiera
country: Latvia
facility: 625
city: Alytus
country: Lithuania
facility: 425
city: Kaunas
country: Lithuania
facility: 427
city: Vilnius
country: Lithuania
facility: 426
city: Guadalajara
country: Mexico
facility: 126
state: Jalisco
city: Guadalajara
country: Mexico
facility: 128
state: Jalisco
city: Aguascalientes
country: Mexico
facility: 129
city: Culiacan
country: Mexico
facility: 127
city: Distrito Federal
country: Mexico
facility: 125
city: Mexico D.F.
country: Mexico
facility: 130
city: Heemstede
country: Netherlands
facility: 401
city: Heeze
country: Netherlands
facility: 400
city: Zwolle
country: Netherlands
facility: 403
city: Bialystok
country: Poland
facility: 475
city: Gdansk
country: Poland
facility: 485
city: Gdansk
country: Poland
facility: 791
city: Katowice
country: Poland
facility: 478
city: Katowice
country: Poland
facility: 480
city: Katowice
country: Poland
facility: 481
city: Krakow
country: Poland
facility: 476
city: Krakow
country: Poland
facility: 793
city: Lublin
country: Poland
facility: 483
city: Poznan
country: Poland
facility: 477
city: Poznan
country: Poland
facility: 479
city: Poznan
country: Poland
facility: 482
city: Warszawa
country: Poland
facility: 488
city: San Juan
country: Puerto Rico
facility: 038
city: Kazan
country: Russian Federation
facility: 501
city: Kazan
country: Russian Federation
facility: 506
city: Moscow
country: Russian Federation
facility: 502
city: Moscow
country: Russian Federation
facility: 503
city: Moscow
country: Russian Federation
facility: 505
city: Nizhny Novgorod
country: Russian Federation
facility: 509
city: Smolensk
country: Russian Federation
facility: 508
city: Badalona
country: Spain
facility: 536
city: Barcelona
country: Spain
facility: 528
city: Barcelona
country: Spain
facility: 529
city: Barcelona
country: Spain
facility: 535
city: Barcelona
country: Spain
facility: 540
city: San Sebastian
country: Spain
facility: 539
city: Santiago de Compostela
country: Spain
facility: 532
city: Valencia
country: Spain
facility: 527
city: Valencia
country: Spain
facility: 537
city: Valladolid
country: Spain
facility: 526
city: Goteborg
country: Sweden
facility: 551
city: Linkoping
country: Sweden
facility: 552
city: Stockholm
country: Sweden
facility: 550
city: Kaohsiung City
country: Taiwan
facility: 806
city: Taichung
country: Taiwan
facility: 801
city: Tainan
country: Taiwan
facility: 800
city: Taoyuan Hsien
country: Taiwan
facility: 803
city: Birmingham
country: United Kingdom
facility: 603
city: Cardiff
country: United Kingdom
facility: 606
city: Cornwall
country: United Kingdom
facility: 601
city: London
country: United Kingdom
facility: 600
city: Middlesborough
country: United Kingdom
facility: 605
city: Newcastle
country: United Kingdom
facility: 607
city: Salford
country: United Kingdom
facility: 608
city: Swansea
country: United Kingdom
facility: 602
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Bresnahan R, Panebianco M, Marson AG. Brivaracetam add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2022 Mar 14;3(3):CD011501. doi: 10.1002/14651858.CD011501.pub3.
citation: 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.
citation: 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.
citation: Markham A. Brivaracetam: First Global Approval. Drugs. 2016 Mar;76(4):517-22. doi: 10.1007/s40265-016-0555-6.