Trial Comparing the Efficacy and Safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR); Initial Monotherapy in Epilepsy; Subjects Aged 16 and Older

NCT ID: NCT01243177

Last Updated: 2021-02-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

888 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-30

Study Completion Date

2015-08-31

Brief Summary

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Compare efficacy and safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR) as monotherapy in newly or recently newly diagnosed subjects with a primary efficacy endpoint of 6-month seizure freedom. Noninferiority design to show a similar risk/benefit balance between Lacosamide (LCM) and Carbamazepine-CR (CBZ-CR).

Detailed Description

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Conditions

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Epilepsy Monotherapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Lacosamide

Group Type EXPERIMENTAL

Lacosamide

Intervention Type DRUG

Lacosamide:

* Strengths: 50 mg / 100 mg
* Form: tablets
* Dosage: total daily target dose of 200 mg, 400 mg or 600 mg. 1 dose reduction was allowed from either 600 mg to 500 mg or from 400 mg to 300 mg total daily dose
* Duration: up to 118 weeks

Carbamazepine-Controlled Release (CBZ-CR)

Group Type ACTIVE_COMPARATOR

Carbamazepine-Controlled Release

Intervention Type DRUG

Carbamazepine-CR:

* Strengths: 200 mg
* Form: tablets
* Dosage: total daily target dose of 400 mg, 800 mg or 1200 mg. 1 dose reduction was allowed from either 1200 mg to 1000 mg or from 800 mg to 600 mg total daily dose
* Duration: up to 118 weeks

Interventions

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Lacosamide

Lacosamide:

* Strengths: 50 mg / 100 mg
* Form: tablets
* Dosage: total daily target dose of 200 mg, 400 mg or 600 mg. 1 dose reduction was allowed from either 600 mg to 500 mg or from 400 mg to 300 mg total daily dose
* Duration: up to 118 weeks

Intervention Type DRUG

Carbamazepine-Controlled Release

Carbamazepine-CR:

* Strengths: 200 mg
* Form: tablets
* Dosage: total daily target dose of 400 mg, 800 mg or 1200 mg. 1 dose reduction was allowed from either 1200 mg to 1000 mg or from 800 mg to 600 mg total daily dose
* Duration: up to 118 weeks

Intervention Type DRUG

Other Intervention Names

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Vimpat® Tegretol® Retard Tablets 200 mg

Eligibility Criteria

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Inclusion Criteria

* Subject able to comply with study requirements
* Subject is 16 years and older (female; male). Minors will be included in countries only if legally permitted
* Subject has newly or recently diagnosed Epilepsy experiencing partial onset seizures (POS) or generalized tonic-clonic seizures with at least 2 unprovoked seizures separated by 48 hours in the 12 months preceding Visit 1 out of which at least 1 seizure occured 3 months preceding Visit 1
* Subject has had an Electroencephalogram (EEG) and a brain Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) exam of the brain within the past 12 months. If the EEG and brain CT scan or MRI exam were not performed prior to Visit 1, they need to be completed and results must be available prior to randomization at Visit 2

Exclusion Criteria

* Subject has a history or presence of seizures of other types than partial-onset (IA, IB, IC with clear focal origin) and generalized tonic-clonic (without clear focal origin) seizures (eg, myoclonic, absence)
* Subject has a history or presence of seizures occurring only in clustered patterns, defined as repeated seizures occurring over a short period of time (ie, \< 20 minutes) with or without function regained between 2 ictal events
* Subject has a history, clinical, or Electroencephalogram (EEG) finding suggestive of Idiopathic Generalized Epilepsy (IGE) at randomization
* Subject has current or previous diagnosis of pseudoseizures, conversion disorders, or other nonepileptic ictal events that could be confused with seizures based on expert opinion and/or EEG evidence
* Subject has any medical or psychiatric condition
* Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening
* Subject has received treatment with Phenobarbital or Primidone within 28 days prior to Visit 1
* Subject is taking Benzodiazepines for a nonepilepsy indication
* Subject has been treated for Epilepsy with any Antiepileptic Drug (AED) (including Benzodiazepines) in the last 6 months before Visit. However, acute and subacute seizure treatment is accepted with a maximum of 2 weeks duration and if treatment was stopped at least 3 days prior to randomization
* Prior use of Felbamate or Vigabatrin is not allowed
* Benzodiazepines as rescue therapy for Epilepsy may have been used as needed in this time period, but not more frequently than once per week
* Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion, has a history of alcohol or drug abuse within the previous 2 years
* Asian ancestry and tests positive for HLA-B\*1502 allele
* Asian ancestry and tests positive for HLA-A\*3101 allele
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eden Sarl

INDUSTRY

Sponsor Role collaborator

UCB BIOSCIENCES GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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UCB Cares

Role: STUDY_DIRECTOR

+1 877 822 9493 (UCB)

Locations

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786

Alabaster, Alabama, United States

Site Status

799

Huntsville, Alabama, United States

Site Status

780

Phoenix, Arizona, United States

Site Status

777

Little Rock, Arkansas, United States

Site Status

795

Ocala, Florida, United States

Site Status

789

Panama City, Florida, United States

Site Status

776

Port Charlotte, Florida, United States

Site Status

779

Manhattan, Kansas, United States

Site Status

874

Charlotte, North Carolina, United States

Site Status

876

Hickory, North Carolina, United States

Site Status

873

Raleigh, North Carolina, United States

Site Status

794

Oklahoma City, Oklahoma, United States

Site Status

881

Mansfield, Texas, United States

Site Status

790

Madison, Wisconsin, United States

Site Status

798

Casper, Wyoming, United States

Site Status

106

East Gosford, New South Wales, Australia

Site Status

109

Randwick, New South Wales, Australia

Site Status

102

Westmead, New South Wales, Australia

Site Status

103

Herston, Queensland, Australia

Site Status

100

Woodville, South Australia, Australia

Site Status

101

Fitzroy, Victoria, Australia

Site Status

108

Heidelberg, Victoria, Australia

Site Status

104

Chatswood, , Australia

Site Status

105

Clayton, , Australia

Site Status

127

Bruges, , Belgium

Site Status

134

Bruges, , Belgium

Site Status

128

Hasselt, , Belgium

Site Status

126

Leuven, , Belgium

Site Status

805

Blagoevgrad, , Bulgaria

Site Status

807

Panagyurishte, , Bulgaria

Site Status

803

Pleven, , Bulgaria

Site Status

810

Rousse, , Bulgaria

Site Status

806

Sofia, , Bulgaria

Site Status

808

Sofia, , Bulgaria

Site Status

811

Sofia, , Bulgaria

Site Status

809

Veliko Tarnovo, , Bulgaria

Site Status

153

St. John's, Newfoundland and Labrador, Canada

Site Status

152

Greenfield Park, Quebec, Canada

Site Status

155

Calgary, , Canada

Site Status

158

Halifax Nova Scotia, , Canada

Site Status

156

Hamilton, , Canada

Site Status

159

Veilleux, , Canada

Site Status

185

Brno, , Czechia

Site Status

190

Ostrava - Vitkovice, , Czechia

Site Status

184

Prague, , Czechia

Site Status

189

Prague, , Czechia

Site Status

180

Zlín, , Czechia

Site Status

205

Helsinki, , Finland

Site Status

207

Kuopio, , Finland

Site Status

236

Nancy, , France

Site Status

233

Paris, , France

Site Status

231

Strasbourg, , France

Site Status

235

Toulouse, , France

Site Status

263

Altenburg, , Germany

Site Status

258

Aschaffenburg, , Germany

Site Status

265

Bad Neustadt an der Saale, , Germany

Site Status

257

Berlin, , Germany

Site Status

262

Berlin, , Germany

Site Status

270

Berlin, , Germany

Site Status

271

Cologne, , Germany

Site Status

260

Göttingen, , Germany

Site Status

269

Leipzig, , Germany

Site Status

256

Marburg, , Germany

Site Status

264

München, , Germany

Site Status

261

Münster, , Germany

Site Status

259

Osnabrück, , Germany

Site Status

496

Alexandroupoli, , Greece

Site Status

495

Ioannina, , Greece

Site Status

493

Thessaloniki, , Greece

Site Status

490

Thessalonikis, , Greece

Site Status

289

Balassagyarmat, , Hungary

Site Status

283

Budapest, , Hungary

Site Status

284

Budapest, , Hungary

Site Status

286

Debrecen, , Hungary

Site Status

282

Győr, , Hungary

Site Status

288

Pécs, , Hungary

Site Status

285

Szeged, , Hungary

Site Status

290

Szekszárd, , Hungary

Site Status

291

Szombathely, , Hungary

Site Status

310

Bari, , Italy

Site Status

309

Modena, , Italy

Site Status

308

Padua, , Italy

Site Status

314

Prato, , Italy

Site Status

311

Roma, , Italy

Site Status

831

Asaka-shi, , Japan

Site Status

833

Hamamatsu, , Japan

Site Status

834

Kagoshima, , Japan

Site Status

844

Kamakura-shi, , Japan

Site Status

846

Kawasaki-shi, , Japan

Site Status

829

Kokubunji-shi, , Japan

Site Status

843

Miyakonojō, , Japan

Site Status

835

Nagoya, , Japan

Site Status

830

Nara, , Japan

Site Status

837

Okayama, , Japan

Site Status

828

Saitama-shi, , Japan

Site Status

836

Sapporo, , Japan

Site Status

847

Sapporo, , Japan

Site Status

832

Shizuoka, , Japan

Site Status

751

Riga, , Latvia

Site Status

727

Alytus, , Lithuania

Site Status

724

Kaunas, , Lithuania

Site Status

728

Vilnius, , Lithuania

Site Status

547

San Luis Potosí City, , Mexico

Site Status

673

Manila, , Philippines

Site Status

672

Pasig, , Philippines

Site Status

676

Quezon City, , Philippines

Site Status

336

Gdansk, , Poland

Site Status

334

Katowice, , Poland

Site Status

340

Katowice, , Poland

Site Status

342

Lublin, , Poland

Site Status

341

Poznan, , Poland

Site Status

338

Szczecin, , Poland

Site Status

343

Warsaw, , Poland

Site Status

360

Coimbra, , Portugal

Site Status

362

Lisbon, , Portugal

Site Status

365

Lisbon, , Portugal

Site Status

366

Porto, , Portugal

Site Status

361

Santa Maria da Feira, , Portugal

Site Status

576

Bucharest, , Romania

Site Status

569

Cluj-Napoca, , Romania

Site Status

578

Craiova, , Romania

Site Status

570

Iași, , Romania

Site Status

579

Iași, , Romania

Site Status

571

Sibiu, , Romania

Site Status

577

Sibiu, , Romania

Site Status

572

Târgu Mureş, , Romania

Site Status

387

Kazan', , Russia

Site Status

389

Kazan', , Russia

Site Status

396

Kirov, , Russia

Site Status

394

Moscow, , Russia

Site Status

401

Moscow, , Russia

Site Status

390

Nizhny Novgorod, , Russia

Site Status

392

Novosibirsk, , Russia

Site Status

397

Saint Petersburg, , Russia

Site Status

400

Saint Petersburg, , Russia

Site Status

386

Smolensk, , Russia

Site Status

399

Yaroslavl, , Russia

Site Status

594

Dolný Kubín, , Slovakia

Site Status

598

Dubnica nad Váhom, , Slovakia

Site Status

596

Hlohovec, , Slovakia

Site Status

600

Krompachy, , Slovakia

Site Status

595

Levoča, , Slovakia

Site Status

599

Tornaľa, , Slovakia

Site Status

601

Žilina, , Slovakia

Site Status

525

Busan, , South Korea

Site Status

521

Daegu, , South Korea

Site Status

518

Dajeon, , South Korea

Site Status

516

Seoul, , South Korea

Site Status

517

Seoul, , South Korea

Site Status

519

Seoul, , South Korea

Site Status

520

Seoul, , South Korea

Site Status

523

Seoul, , South Korea

Site Status

524

Seoul, , South Korea

Site Status

422

Badalona, , Spain

Site Status

413

Barcelona, , Spain

Site Status

418

Donostia / San Sebastian, , Spain

Site Status

416

Madrid, , Spain

Site Status

425

Madrid, , Spain

Site Status

426

Madrid, , Spain

Site Status

421

Murcia (El Palmar), , Spain

Site Status

419

San Cristóbal de La Laguna, , Spain

Site Status

414

Santiago de Compostela, , Spain

Site Status

424

Seville, , Spain

Site Status

440

Gothenburg, , Sweden

Site Status

438

Stockholm, , Sweden

Site Status

442

Umeå, , Sweden

Site Status

651

Aarau, , Switzerland

Site Status

654

Biel, , Switzerland

Site Status

653

Lugano, , Switzerland

Site Status

647

Sankt Gallen, , Switzerland

Site Status

699

Bangkok, , Thailand

Site Status

702

Bangkok, , Thailand

Site Status

703

Bangkok, , Thailand

Site Status

698

Khon Kaen, , Thailand

Site Status

622

Chernihiv, , Ukraine

Site Status

628

Dnipropetrovsk, , Ukraine

Site Status

626

Kharkiv, , Ukraine

Site Status

621

Luhansk, , Ukraine

Site Status

625

Odesa, , Ukraine

Site Status

632

Simferopol, , Ukraine

Site Status

633

Vinnytsa, , Ukraine

Site Status

466

Birmingham, , United Kingdom

Site Status

472

Glasgow, , United Kingdom

Site Status

471

Stoke-on-Trent, , United Kingdom

Site Status

Countries

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United States Australia Belgium Bulgaria Canada Czechia Finland France Germany Greece Hungary Italy Japan Latvia Lithuania Mexico Philippines Poland Portugal Romania Russia Slovakia South Korea Spain Sweden Switzerland Thailand Ukraine United Kingdom

References

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Baulac M, Rosenow F, Toledo M, Terada K, Li T, De Backer M, Werhahn KJ, Brock M. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol. 2017 Jan;16(1):43-54. doi: 10.1016/S1474-4422(16)30292-7. Epub 2016 Nov 24.

Reference Type RESULT
PMID: 27889312 (View on PubMed)

Mintzer S, Dimova S, Zhang Y, Steiniger-Brach B, De Backer M, Chellun D, Roebling R. Effects of lacosamide and carbamazepine on lipids in a randomized trial. Epilepsia. 2020 Dec;61(12):2696-2704. doi: 10.1111/epi.16745. Epub 2020 Nov 17.

Reference Type RESULT
PMID: 33200428 (View on PubMed)

Lindauer A, Laveille C, Stockis A. Time-to-Seizure Modeling of Lacosamide Used in Monotherapy in Patients with Newly Diagnosed Epilepsy. Clin Pharmacokinet. 2017 Nov;56(11):1403-1413. doi: 10.1007/s40262-017-0530-8.

Reference Type DERIVED
PMID: 28290119 (View on PubMed)

Related Links

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Other Identifiers

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2010-019765-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SP0993

Identifier Type: -

Identifier Source: org_study_id

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