MedPath

Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures

Phase 3
Completed
Conditions
Epilepsy
Interventions
Drug: Placebo
Drug: Antiepileptic drugs with market authorization available per country
Registration Number
NCT01261325
Lead Sponsor
UCB Pharma
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
768
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboMatching placebo tablets administered twice daily
PlaceboAntiepileptic drugs with market authorization available per countryMatching placebo tablets administered twice daily
Brivaracetam 100 mg/ dayAntiepileptic drugs with market authorization available per countryBrivaracetam 50 mg/ day administered twice daily.
Brivaracetam 200 mg/ dayAntiepileptic drugs with market authorization available per countryBrivaracetam 100 mg/ day administered twice daily
Brivaracetam 100 mg/ dayBrivaracetamBrivaracetam 50 mg/ day administered twice daily.
Brivaracetam 200 mg/ dayBrivaracetamBrivaracetam 100 mg/ day administered twice daily
Primary Outcome Measures
NameTimeMethod
Percent Reduction Over Placebo for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration12 week Treatment Period

Primary endpoint: United States of America (FDA)

50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day DurationBaseline to 12 week Treatment Period

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.

Secondary Outcome Measures
NameTimeMethod
Percent Change in Partial Onset Seizure (Type I) Frequency From the Baseline to the Treatment PeriodBaseline to 12 week Treatment Period
Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment PeriodBaseline to 12 week Treatment Period
Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period12 week Treatment Period
All Seizure Frequency (Type I + II + III) During the 12-week Treatment Period12 week Treatment Period
Time to the First Type I Seizure During the Treatment Period12 week Treatment Period
Time to the Fifth Type I Seizure During the Treatment Period12 week Treatment Period
Time to the Tenth Type I Seizure During the Treatment Period12 week Treatment Period

Trial Locations

Locations (207)

090

🇺🇸

Ocala, Florida, United States

006

🇺🇸

Tucson, Arizona, United States

044

🇺🇸

Sarasota, Florida, United States

071

🇺🇸

Miami, Florida, United States

073

🇺🇸

Naples, Florida, United States

051

🇺🇸

Missoula, Montana, United States

200

🇦🇹

Wien, Austria

902

🇩🇪

Erlangen, Germany

275

🇫🇮

Kuopio, Finland

305

🇫🇷

Montpellier, France

329

🇩🇪

Berlin, Germany

327

🇩🇪

Kiel, Germany

900

🇩🇪

Marburg, Germany

852

🇯🇵

Itami-city, Japan

382

🇮🇹

Torino, Italy

850

🇯🇵

Osaka, Japan

411

🇭🇺

Budapest, Hungary

700

🇭🇰

Shatin, Hong Kong

384

🇮🇹

Reggio Calabria, Italy

851

🇯🇵

Shizuoka, Japan

427

🇱🇹

Kaunas, Lithuania

125

🇲🇽

Distrito Federal, Mexico

793

🇵🇱

Krakow, Poland

038

🇵🇷

San Juan, Puerto Rico

501

🇷🇺

Kazan, Russian Federation

505

🇷🇺

Moscow, Russian Federation

482

🇵🇱

Poznan, Poland

502

🇷🇺

Moscow, Russian Federation

503

🇷🇺

Moscow, Russian Federation

509

🇷🇺

Nizhny Novgorod, Russian Federation

806

🇨🇳

Kaohsiung City, Taiwan

801

🇨🇳

Taichung, Taiwan

803

🇨🇳

Taoyuan Hsien, Taiwan

064

🇺🇸

Port Charlotte, Florida, United States

110

🇺🇸

Miami, Florida, United States

025

🇺🇸

San Francisco, California, United States

085

🇺🇸

Colorado Springs, Colorado, United States

009

🇺🇸

Golden Valley, Minnesota, United States

089

🇺🇸

Casper, Wyoming, United States

013

🇺🇸

Phoenix, Arizona, United States

410

🇭🇺

Budapest, Hungary

412

🇭🇺

Budapest, Hungary

001

🇺🇸

Phoenix, Arizona, United States

775

🇺🇸

Little Rock, Arkansas, United States

069

🇺🇸

Iowa City, Iowa, United States

070

🇺🇸

Columbus, Ohio, United States

049

🇺🇸

Houston, Texas, United States

091

🇺🇸

Oklahoma City, Oklahoma, United States

005

🇺🇸

Peoria, Illinois, United States

226

🇧🇪

Hechteleksel, Belgium

048

🇺🇸

Rome, Georgia, United States

095

🇺🇸

Kingston, New York, United States

068

🇺🇸

Waldorf, Maryland, United States

021

🇺🇸

Port Royal, South Carolina, United States

058

🇺🇸

Voorhees, New Jersey, United States

062

🇺🇸

Columbus, Georgia, United States

039

🇺🇸

Boise, Idaho, United States

023

🇺🇸

Atlanta, Georgia, United States

042

🇺🇸

Hamilton, New Jersey, United States

022

🇺🇸

New York, New York, United States

032

🇺🇸

Lebanon, New Hampshire, United States

294

🇧🇬

Blagoevrad, Bulgaria

653

🇪🇪

Tallinn, Estonia

651

🇪🇪

Tartu, Estonia

076

🇨🇦

Toronto, Ontario, Canada

099

🇺🇸

New York, New York, United States

252

🇨🇿

Praha 1, Czechia

034

🇺🇸

Cleveland, Ohio, United States

015

🇺🇸

Philadelphia, Pennsylvania, United States

003

🇺🇸

Durham, North Carolina, United States

098

🇺🇸

Poughkeepsie, New York, United States

227

🇧🇪

Leuven, Belgium

078

🇨🇦

London, Ontario, Canada

054

🇺🇸

Tulsa, Oklahoma, United States

096

🇺🇸

Canton, Ohio, United States

228

🇧🇪

Liege, Belgium

043

🇺🇸

Oklahoma City, Oklahoma, United States

052

🇺🇸

Madison, Wisconsin, United States

916

🇨🇿

Kromeriz, Czechia

202

🇦🇹

Innsbruck, Austria

104

🇧🇷

Belo Horizonte, Brazil

103

🇧🇷

Riberao Preto, Brazil

080

🇨🇦

Saskatoon, Saskatchewan, Canada

100

🇧🇷

Florianopolis, Brazil

101

🇧🇷

Sao Paulo, Brazil

077

🇨🇦

Greenfield Park, Quebec, Canada

650

🇪🇪

Tallinn, Estonia

652

🇪🇪

Tallinn, Estonia

278

🇫🇮

Oulu, Finland

287

🇧🇬

Sofiya, Bulgaria

075

🇨🇦

Calgary, Alberta, Canada

256

🇨🇿

Ostrava, Czechia

301

🇫🇷

Bethune, France

326

🇩🇪

Bernau, Germany

331

🇩🇪

Goettingen, Germany

277

🇫🇮

Turku, Finland

308

🇫🇷

Marseille, France

904

🇩🇪

Kehl-Kork, Germany

276

🇫🇮

Tampere, Finland

332

🇩🇪

Bielefeld, Germany

334

🇩🇪

Osnabruck, Germany

413

🇭🇺

Kecskemet, Hungary

728

🇮🇳

Mumbai, Maharastra, India

377

🇮🇹

Monserrato, Cagliari, Italy

386

🇮🇹

Napoli, Italy

375

🇮🇹

Pisa, Italy

330

🇩🇪

Ravensburg, Germany

414

🇭🇺

Debrecen, Hungary

726

🇮🇳

Bangalore, India

729

🇮🇳

Madurai, India

380

🇮🇹

Firenze, Italy

731

🇮🇳

Nashik, Maharashtra, India

328

🇩🇪

Ulm, Germany

727

🇮🇳

Hyderabad, Andhra Pradesh, India

725

🇮🇳

Mumbai, Maharastra, India

378

🇮🇹

Bari, Italy

376

🇮🇹

Perugia, Italy

383

🇮🇹

Pozzilli, Italy

752

🇰🇷

Gwangju, Korea, Republic of

425

🇱🇹

Alytus, Lithuania

601

🇬🇧

Cornwall, United Kingdom

855

🇯🇵

Hiroshima, Japan

854

🇯🇵

Yokohama-City, Japan

753

🇰🇷

Busan, Korea, Republic of

627

🇱🇻

Daugapils, Latvia

629

🇱🇻

Jekabpils, Latvia

400

🇳🇱

Heeze, Netherlands

126

🇲🇽

Guadalajara, Jalisco, Mexico

750

🇰🇷

Seoul, Korea, Republic of

625

🇱🇻

Valmiera, Latvia

129

🇲🇽

Aguascalientes, Mexico

130

🇲🇽

Mexico D.F., Mexico

477

🇵🇱

Poznan, Poland

508

🇷🇺

Smolensk, Russian Federation

751

🇰🇷

Seoul, Korea, Republic of

626

🇱🇻

Riga, Latvia

628

🇱🇻

Riga, Latvia

127

🇲🇽

Culiacan, Mexico

537

🇪🇸

Valencia, Spain

403

🇳🇱

Zwolle, Netherlands

791

🇵🇱

Gdansk, Poland

481

🇵🇱

Katowice, Poland

552

🇸🇪

Linkoping, Sweden

606

🇬🇧

Cardiff, United Kingdom

754

🇰🇷

Seoul, Korea, Republic of

401

🇳🇱

Heemstede, Netherlands

475

🇵🇱

Bialystok, Poland

485

🇵🇱

Gdansk, Poland

480

🇵🇱

Katowice, Poland

476

🇵🇱

Krakow, Poland

536

🇪🇸

Badalona, Spain

478

🇵🇱

Katowice, Poland

479

🇵🇱

Poznan, Poland

800

🇨🇳

Tainan, Taiwan

540

🇪🇸

Barcelona, Spain

600

🇬🇧

London, United Kingdom

603

🇬🇧

Birmingham, United Kingdom

529

🇪🇸

Barcelona, Spain

605

🇬🇧

Middlesborough, United Kingdom

607

🇬🇧

Newcastle, United Kingdom

608

🇬🇧

Salford, United Kingdom

602

🇬🇧

Swansea, United Kingdom

539

🇪🇸

San Sebastian, Spain

527

🇪🇸

Valencia, Spain

532

🇪🇸

Santiago de Compostela, Spain

528

🇪🇸

Barcelona, Spain

020

🇺🇸

Ames, Iowa, United States

063

🇺🇸

Atlanta, Georgia, United States

010

🇺🇸

Asheville, North Carolina, United States

061

🇺🇸

Austin, Texas, United States

002

🇺🇸

Toledo, Ohio, United States

050

🇺🇸

Arlington, Texas, United States

035

🇺🇸

Dallas, Texas, United States

033

🇺🇸

Seattle, Washington, United States

253

🇨🇿

Praha 4, Czechia

250

🇨🇿

Zlin, Czechia

913

🇨🇿

Ostrava Poruba, Czechia

060

🇺🇸

Aurora, Colorado, United States

045

🇺🇸

Sacramento, California, United States

027

🇺🇸

Orlando, Florida, United States

017

🇺🇸

Winfield, Illinois, United States

092

🇺🇸

Hammond, Louisiana, United States

780

🇺🇸

Lexington, Kentucky, United States

055

🇺🇸

East Lansing, Michigan, United States

008

🇺🇸

Bethesda, Maryland, United States

203

🇦🇹

Wien, Austria

056

🇺🇸

Spokane, Washington, United States

057

🇺🇸

Milwaukee, Wisconsin, United States

011

🇺🇸

Dallas, Texas, United States

201

🇦🇹

Linz, Austria

286

🇧🇬

Sofiya, Bulgaria

036

🇺🇸

Charlottesville, Virginia, United States

079

🇨🇦

Montreal, Quebec, Canada

251

🇨🇿

Ostrava, Czechia

335

🇩🇪

Muenchen, Germany

379

🇮🇹

Milano, Italy

426

🇱🇹

Vilnius, Lithuania

483

🇵🇱

Lublin, Poland

128

🇲🇽

Guadalajara, Jalisco, Mexico

488

🇵🇱

Warszawa, Poland

551

🇸🇪

Goteborg, Sweden

526

🇪🇸

Valladolid, Spain

506

🇷🇺

Kazan, Russian Federation

550

🇸🇪

Stockholm, Sweden

535

🇪🇸

Barcelona, Spain

028

🇺🇸

Charleston, South Carolina, United States

701

🇭🇰

Hong Kong, Hong Kong

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