NCT01261325

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
768

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Dec 2010

Typical duration for phase_3

Geographic Reach
27 countries

203 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2010

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

December 9, 2010

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 16, 2010

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
2.3 years until next milestone

Results Posted

Study results publicly available

August 15, 2016

Completed
Last Updated

July 22, 2022

Status Verified

July 1, 2022

Enrollment Period

3.4 years

First QC Date

December 9, 2010

Results QC Date

March 14, 2016

Last Update Submit

July 14, 2022

Conditions

Keywords

EpilepsyBrivaracetamPartial Onset SeizuresAdjunctive treatment

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (7)

  • 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

  • +2 more secondary outcomes

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Matching placebo tablets administered twice daily

Drug: PlaceboDrug: Antiepileptic drugs with market authorization available per country

Brivaracetam 100 mg/ day

EXPERIMENTAL

Brivaracetam 50 mg/ day administered twice daily.

Drug: BrivaracetamDrug: Antiepileptic drugs with market authorization available per country

Brivaracetam 200 mg/ day

EXPERIMENTAL

Brivaracetam 100 mg/ day administered twice daily

Drug: BrivaracetamDrug: Antiepileptic drugs with market authorization available per country

Interventions

Daily oral dose of two equal intakes of placebo in a double-blinded way for the 12-week treatment period

Placebo

Daily oral dose of two equal intakes of Brivaracetam 100 mg/ day in a double-blinded way for the 12-week treatment period

Brivaracetam 100 mg/ day
Brivaracetam 100 mg/ dayBrivaracetam 200 mg/ dayPlacebo

Eligibility Criteria

Age16 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (207)

001

Phoenix, Arizona, United States

Location

013

Phoenix, Arizona, United States

Location

006

Tucson, Arizona, United States

Location

775

Little Rock, Arkansas, United States

Location

045

Sacramento, California, United States

Location

025

San Francisco, California, United States

Location

060

Aurora, Colorado, United States

Location

085

Colorado Springs, Colorado, United States

Location

071

Miami, Florida, United States

Location

110

Miami, Florida, United States

Location

073

Naples, Florida, United States

Location

090

Ocala, Florida, United States

Location

027

Orlando, Florida, United States

Location

064

Port Charlotte, Florida, United States

Location

044

Sarasota, Florida, United States

Location

023

Atlanta, Georgia, United States

Location

063

Atlanta, Georgia, United States

Location

062

Columbus, Georgia, United States

Location

048

Rome, Georgia, United States

Location

039

Boise, Idaho, United States

Location

005

Peoria, Illinois, United States

Location

017

Winfield, Illinois, United States

Location

020

Ames, Iowa, United States

Location

069

Iowa City, Iowa, United States

Location

780

Lexington, Kentucky, United States

Location

092

Hammond, Louisiana, United States

Location

008

Bethesda, Maryland, United States

Location

068

Waldorf, Maryland, United States

Location

055

East Lansing, Michigan, United States

Location

009

Golden Valley, Minnesota, United States

Location

051

Missoula, Montana, United States

Location

032

Lebanon, New Hampshire, United States

Location

042

Hamilton, New Jersey, United States

Location

058

Voorhees Township, New Jersey, United States

Location

095

Kingston, New York, United States

Location

022

New York, New York, United States

Location

099

New York, New York, United States

Location

098

Poughkeepsie, New York, United States

Location

010

Asheville, North Carolina, United States

Location

003

Durham, North Carolina, United States

Location

096

Canton, Ohio, United States

Location

034

Cleveland, Ohio, United States

Location

070

Columbus, Ohio, United States

Location

002

Toledo, Ohio, United States

Location

043

Oklahoma City, Oklahoma, United States

Location

091

Oklahoma City, Oklahoma, United States

Location

054

Tulsa, Oklahoma, United States

Location

015

Philadelphia, Pennsylvania, United States

Location

028

Charleston, South Carolina, United States

Location

021

Port Royal, South Carolina, United States

Location

050

Arlington, Texas, United States

Location

061

Austin, Texas, United States

Location

011

Dallas, Texas, United States

Location

035

Dallas, Texas, United States

Location

049

Houston, Texas, United States

Location

036

Charlottesville, Virginia, United States

Location

033

Seattle, Washington, United States

Location

056

Spokane, Washington, United States

Location

052

Madison, Wisconsin, United States

Location

057

Milwaukee, Wisconsin, United States

Location

089

Casper, Wyoming, United States

Location

202

Innsbruck, Austria

Location

201

Linz, Austria

Location

200

Vienna, Austria

Location

203

Vienna, Austria

Location

226

Hechteleksel, Belgium

Location

227

Leuven, Belgium

Location

228

Liège, Belgium

Location

104

Belo Horizonte, Brazil

Location

100

Florianópolis, Brazil

Location

103

Riberao Preto, Brazil

Location

101

São Paulo, Brazil

Location

294

Blagoevrad, Bulgaria

Location

286

Sofia, Bulgaria

Location

287

Sofia, Bulgaria

Location

075

Calgary, Alberta, Canada

Location

078

London, Ontario, Canada

Location

076

Toronto, Ontario, Canada

Location

077

Greenfield Park, Quebec, Canada

Location

079

Montreal, Quebec, Canada

Location

080

Saskatoon, Saskatchewan, Canada

Location

916

Kroměříž, Czechia

Location

251

Ostrava, Czechia

Location

256

Ostrava, Czechia

Location

913

Ostrava Poruba, Czechia

Location

252

Prague, Czechia

Location

253

Prague, Czechia

Location

250

Zlín, Czechia

Location

650

Tallinn, Estonia

Location

652

Tallinn, Estonia

Location

653

Tallinn, Estonia

Location

651

Tartu, Estonia

Location

275

Kuopio, Finland

Location

278

Oulu, Finland

Location

276

Tampere, Finland

Location

277

Turku, Finland

Location

301

Béthune, France

Location

308

Marseille, France

Location

305

Montpellier, France

Location

329

Berlin, Germany

Location

326

Bernau, Germany

Location

332

Bielefeld, Germany

Location

902

Erlangen, Germany

Location

331

Göttingen, Germany

Location

904

Kehl-Kork, Germany

Location

327

Kiel, Germany

Location

900

Marburg, Germany

Location

335

München, Germany

Location

334

Osnabrück, Germany

Location

330

Ravensburg, Germany

Location

328

Ulm, Germany

Location

701

Hong Kong, Hong Kong

Location

700

Shatin, Hong Kong

Location

410

Budapest, Hungary

Location

411

Budapest, Hungary

Location

412

Budapest, Hungary

Location

414

Debrecen, Hungary

Location

413

Kecskemét, Hungary

Location

727

Hyderabad, Andhra Pradesh, India

Location

725

Mumbai, Maharashtra, India

Location

728

Mumbai, Maharashtra, India

Location

731

Nashik, Maharashtra, India

Location

726

Bangalore, India

Location

729

Madurai, India

Location

377

Monserrato, Cagliari, Italy

Location

378

Bari, Italy

Location

380

Florence, Italy

Location

379

Milan, Italy

Location

386

Napoli, Italy

Location

376

Perugia, Italy

Location

375

Pisa, Italy

Location

383

Pozzilli, Italy

Location

384

Reggio Calabria, Italy

Location

382

Torino, Italy

Location

855

Hiroshima, Japan

Location

852

Itami, Japan

Location

850

Osaka, Japan

Location

851

Shizuoka, Japan

Location

854

Yokohama, Japan

Location

627

Daugapils, Latvia

Location

629

Jēkabpils, Latvia

Location

626

Riga, Latvia

Location

628

Riga, Latvia

Location

625

Valmiera, Latvia

Location

425

Alytus, Lithuania

Location

427

Kaunas, Lithuania

Location

426

Vilnius, Lithuania

Location

126

Guadalajara, Jalisco, Mexico

Location

128

Guadalajara, Jalisco, Mexico

Location

129

Aguascalientes, Mexico

Location

127

Culiacán, Mexico

Location

125

Distrito Federal, Mexico

Location

130

Mexico City, Mexico

Location

401

Heemstede, Netherlands

Location

400

Heeze, Netherlands

Location

403

Zwolle, Netherlands

Location

475

Bialystok, Poland

Location

485

Gdansk, Poland

Location

791

Gdansk, Poland

Location

478

Katowice, Poland

Location

480

Katowice, Poland

Location

481

Katowice, Poland

Location

476

Krakow, Poland

Location

793

Krakow, Poland

Location

483

Lublin, Poland

Location

477

Poznan, Poland

Location

479

Poznan, Poland

Location

482

Poznan, Poland

Location

488

Warsaw, Poland

Location

038

San Juan, Puerto Rico

Location

501

Kazan', Russia

Location

506

Kazan', Russia

Location

502

Moscow, Russia

Location

503

Moscow, Russia

Location

505

Moscow, Russia

Location

509

Nizhny Novgorod, Russia

Location

508

Smolensk, Russia

Location

753

Busan, South Korea

Location

752

Gwangju, South Korea

Location

750

Seoul, South Korea

Location

751

Seoul, South Korea

Location

754

Seoul, South Korea

Location

536

Badalona, Spain

Location

528

Barcelona, Spain

Location

529

Barcelona, Spain

Location

535

Barcelona, Spain

Location

540

Barcelona, Spain

Location

539

Donostia / San Sebastian, Spain

Location

532

Santiago de Compostela, Spain

Location

527

Valencia, Spain

Location

537

Valencia, Spain

Location

526

Valladolid, Spain

Location

551

Gothenburg, Sweden

Location

552

Linköping, Sweden

Location

550

Stockholm, Sweden

Location

806

Kaohsiung City, Taiwan

Location

801

Taichung, Taiwan

Location

800

Tainan, Taiwan

Location

803

Taoyuan Hsien, Taiwan

Location

603

Birmingham, United Kingdom

Location

606

Cardiff, United Kingdom

Location

601

Cornwall, United Kingdom

Location

600

London, United Kingdom

Location

605

Middlesbrough, United Kingdom

Location

607

Newcastle, United Kingdom

Location

608

Salford, United Kingdom

Location

602

Swansea, United Kingdom

Location

Related Publications (18)

  • 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.

  • 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.

  • Brandt C, Dimova S, Elmoufti S, Laloyaux C, Nondonfaz X, Klein P. Retention, efficacy, tolerability, and quality of life during long-term adjunctive brivaracetam treatment by number of lifetime antiseizure medications: A post hoc analysis of phase 3 trials in adults with focal seizures. Epilepsy Behav. 2023 Jan;138:108967. doi: 10.1016/j.yebeh.2022.108967. Epub 2022 Nov 23.

  • 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.

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Epilepsy

Interventions

brivaracetamAnticonvulsants

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Central Nervous System AgentsTherapeutic UsesPharmacologic ActionsChemical Actions and Uses

Results Point of Contact

Title
Study Director
Organization
UCB Clinical Trial Call Center

Study Officials

  • UCB Clinical Trial Call Center

    +1 877 822 9493 (UCB)

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

December 9, 2010

First Posted

December 16, 2010

Study Start

December 1, 2010

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

July 22, 2022

Results First Posted

August 15, 2016

Record last verified: 2022-07

Locations