Study to Investigate Lacosamide as Add-on Therapy in Subjects ≥4 Years to <17 Years of Age With Partial Onset Seizures

NCT ID: NCT01921205

Last Updated: 2018-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 404 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-29
• Study Completion Date: 2017-01-24

Brief Summary

Study to evaluate the efficacy of Lacosamide (LCM) administered in addition to 1 to ≤3 other Anti-Epileptic Drugs in subjects with epilepsy ≥4 years to <17 years of age who currently have uncontrolled partial onset seizures.

Detailed Description

The primary objective of this study is to evaluate the efficacy of LCM administered concomitantly with 1 to ≤3 Anti-Epileptic Drugs (AEDs) in subjects with epilepsy ≥4 years to <17 years of age who currently have uncontrolled partial onset seizures.

The secondary objective is to evaluate the safety and tolerability of LCM in subjects ≥4 years to <17 years of age.

An additional objective is to evaluate the pharmacokinetics (PK) of LCM in subjects ≥4 years to <17 years of age.

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lacosamide

Group Type: EXPERIMENTAL

Lacosamide

Intervention Type: DRUG

Subjects <30 kg (LCM oral solution): 4 mg/kg - 6 mg/kg BID ( 8mg/kg/day - 12 mg/kg/day)

Subjects ≥30 kg to <50 kg (LCM oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)

Subjects ≥50 kg (LCM tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Subjects <30 kg (placebo oral solution): 4 mg/kg - 6 mg/kg BID (8 mg/kg/day - 12 mg/kg/day)

Subjects ≥30 kg to <50 kg (placebo oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)

Subjects ≥50 kg (placebo tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)

Interventions

Lacosamide

Subjects <30 kg (LCM oral solution): 4 mg/kg - 6 mg/kg BID ( 8mg/kg/day - 12 mg/kg/day)

Subjects ≥30 kg to <50 kg (LCM oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)

Subjects ≥50 kg (LCM tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)

Intervention Type: DRUG

Placebo

Subjects <30 kg (placebo oral solution): 4 mg/kg - 6 mg/kg BID (8 mg/kg/day - 12 mg/kg/day)

Subjects ≥30 kg to <50 kg (placebo oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)

Subjects ≥50 kg (placebo tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)

Intervention Type: OTHER

Other Intervention Names

Vimpat(R)

Eligibility Criteria

Inclusion Criteria

• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the parent(s) or legal representative. The Informed Consent form or a specific Assent form, where required, will be signed and dated by minors
• Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator
• Subject is male or female from ≥4 years to <17 years of age
• Subject has a diagnosis of Epilepsy with partial-onset seizures. The results of ≥1 prior electroencephalogram (EEG) AND 1 prior magnetic resonance imaging/computerized tomography scan should be consistent with the above diagnosis
• Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with ≥2 Anti-Epileptic Drugs (AEDs) (concurrently or sequentially)
• Subject must have been observed to have on average ≥2 partial onset seizures per 28 days with seizure free phase no longer than 21 days in the 8 week period prior to entry into the Baseline Period. During this study, subjects must have reported ≥2 partial onset seizures during the 8 week prospective Baseline Period to be eligible for randomization at Visit 2. (Note: In the case of simple partial onset seizures, only those seizures with motor signs will be counted towards meeting the inclusion criterion.)
• Subject is on a stable dosage regimen of 1 to ≤3 AEDs. The daily dosage regimen of concomitant AED therapy must be kept constant for a period of ≥4 weeks prior to the Baseline Period
• Vagal nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED. The VNS device must be implanted for ≥6 months before Visit 1, and the device settings must be stable for ≥4 weeks before Visit 1 and be kept stable during the Baseline Period. Use of the VNS device magnet is allowed

Exclusion Criteria

• Subject has previously participated in this study or subject has been assigned to Lacosamide (LCM) in a previous LCM study
• Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within ≤2 months of Visit 1 or is currently participating in another study of an IMP or a medical device
• Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study
• Subject ≥6 years of age 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 a known hypersensitivity to any component of the IMP or has ever received LCM
• Female subject who is pregnant or nursing, and/or a female subject of childbearing potential who is not surgically sterile or does not practice 1 highly effective method of contraception (according to International Conference on Harmonisation [ICH] guidance defined as those that result in a failure rate of less than 1% per year when used consistently and correctly), unless sexually abstinent, for the duration of the study. Female subject of childbearing potential taking enzyme inducing antiepileptic drugs (EI AEDs: carbamazepine, phenytoin, barbiturates, primidone, topiramate, oxcarbazepine) who is not surgically sterile or does not practice 1 highly effective method of contraception according to the WHO recommendation (ie, depot medroxyprogesterone acetate, norethisterone enantate, intrauterine devices, combined injectables, and progestogen implants) with administration of EI AEDs OR does not practice 2 combined methods of contraception (ie, combined hormonal contraception plus barrier method with spermicidal agent), unless sexually abstinent, for the duration of the study
• Subject has a medical condition that could be expected in the opinion of the investigator to interfere with drug absorption, distribution, metabolism, or excretion
• Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in addition to other unprovoked seizures is not exclusionary
• Subject is on a ketogenic or other specialized diet. If the subject was on a specialized diet in the past, they must be off the diet for ≥2 months prior to the Baseline Period
• Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level ≥2 times the upper limit of normal (ULN), or creatinine clearance less than 30 mL/min
• Subject has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, second or third degree heart block at rest or a corrected QT interval [QTc] greater than 450 ms)
• Subject has hemodynamically significant congenital heart disease
• Subject has an arrhythmic heart condition requiring medical therapy
• Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias
• Subject has nonepileptic events that could be confused with seizures
• Subject has a current diagnosis of Lennox-Gastaut syndrome, primary generalized epilepsy, mixed seizure disorder (partial and primarily generalized seizures), or purely nocturnal seizures
• Subject has a history of convulsive status epilepticus ≤2 months prior to the Baseline Period
• Subject has been treated with vigabatrin and experienced any vision loss. Subjects who have received vigabatrin in the past must have documentation of an assessment for vision loss prior to study entry or documentation of why visual field testing cannot be performed
• Subject has been treated with felbamate and has experienced any serious toxicity issues (defined as liver failure, aplastic anemia) with this treatment. Subjects treated with felbamate for <12 months are excluded. Note: any subject who has been treated with felbamate for ≥12 months and has not experienced serious toxicity issues is eligible
• Subject has a medically documented history of alcohol or drug abuse
• Subject has a known cardiac sodium channelopathy, such as Brugada syndrome
• Subject has an acute or sub acutely progressive central nervous system disease. Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease (malignant brain tumor or Rasmussen Syndrome)

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

UCB Cares

Role: STUDY_DIRECTOR

+1 877 822 9493

Locations

127

Boulder, Colorado, United States

105

Orlando, Florida, United States

117

Tampa, Florida, United States

103

Atlanta, Georgia, United States

124

Lexington, Kentucky, United States

112

Louisville, Kentucky, United States

121

Shreveport, Louisiana, United States

115

Las Vegas, Nevada, United States

102

Charlotte, North Carolina, United States

640

Eugene, Oregon, United States

122

Dallas, Texas, United States

101

Tomball, Texas, United States

114

Seattle, Washington, United States

143

Buenos Aires, , Argentina

142

Córdoba, , Argentina

200

Heidelberg West, , Australia

203

Herston, , Australia

205

South Brisbane, , Australia

304

Brussels, , Belgium

310

Sofia, , Bulgaria

312

Sofia, , Bulgaria

172

Floridablanca, , Colombia

171

Medellín, , Colombia

613

Osijek, , Croatia

610

Rijeka, , Croatia

612

Zagreb, , Croatia

321

Hradec Králové, , Czechia

320

Ostrava-Poruba, , Czechia

322

Prague, , Czechia

323

Prague, , Czechia

331

Tallinn, , Estonia

330

Tartu, , Estonia

620

Tbilisi, , Georgia

621

Tbilisi, , Georgia

622

Tbilisi, , Georgia

623

Tbilisi, , Georgia

361

Budapest, , Hungary

362

Budapest, , Hungary

363

Budapest, , Hungary

364

Budapest, , Hungary

360

Debrecen, , Hungary

367

Miskolc, , Hungary

366

Pécs, , Hungary

370

Holon, , Israel

371

Kfar Saba, , Israel

374

Petah Tikva, , Israel

372

Tel Aviv, , Israel

384

Bologna, , Italy

388

Florence, , Italy

387

Genova, , Italy

380

Mantova, , Italy

381

Milan, , Italy

393

Padua, , Italy

383

Roma, , Italy

392

Roma, , Italy

386

Verona, , Italy

400

Riga, , Latvia

402

Valmiera, , Latvia

411

Kaunas, , Lithuania

569

Culiacán, , Mexico

563

Guadalajara, , Mexico

568

Monterrey, , Mexico

660

Podgorica, , Montenegro

433

Gdansk, , Poland

432

Katowice, , Poland

420

Kielce, , Poland

422

Krakow, , Poland

431

Krakow, , Poland

423

Poznan, , Poland

425

Poznan, , Poland

421

Szczecin, , Poland

429

Tyniec Mały, , Poland

430

Warsaw, , Poland

428

Wroclaw, , Poland

574

Bucharest, , Romania

572

Cluj-Napoca, , Romania

576

Sibiu, , Romania

580

Suceava, , Romania

570

Timișoara, , Romania

577

Timișoara, , Romania

443

Kazan', , Russia

444

Kazan', , Russia

442

Moscow, , Russia

449

Moscow, , Russia

441

Saint Petersburg, , Russia

446

Saint Petersburg, , Russia

440

Smolensk, , Russia

447

Voronezh, , Russia

464

Belgrade, , Serbia

460

Kragujevac, , Serbia

461

New Belgrade, , Serbia

462

Novi Sad, , Serbia

463

Novi Sad, , Serbia

470

Bardejov, , Slovakia

473

Nitra, , Slovakia

472

Nové Zámky, , Slovakia

670

Ljubljana, , Slovenia

211

Daegu, , South Korea

210

Seoul, , South Korea

212

Seoul, , South Korea

213

Seoul, , South Korea

215

Seoul, , South Korea

220

Changhua, , Taiwan

222

Taichung, , Taiwan

224

Taipei, , Taiwan

232

Bangkok, , Thailand

236

Bangkoknoi, , Thailand

231

Muang, , Thailand

233

Muang, , Thailand

235

Pathumwan, , Thailand

230

Ratchathewi, , Thailand

602

Dnipropetrovsk, , Ukraine

606

Kiev, , Ukraine

682

Uzhhorod, , Ukraine

603

Vinnitsa, , Ukraine

514

Birmingham, , United Kingdom

515

Birmingham, , United Kingdom

511

Leeds, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Bulgaria; Colombia; Croatia; Czechia; Estonia; Georgia; Hungary; Israel; Italy; Latvia; Lithuania; Mexico; Montenegro; Poland; Romania; Russia; Serbia; Slovakia; Slovenia; South Korea; Taiwan; Thailand; Ukraine; United Kingdom

References

Johnson ME, McClung C, Bozorg AM. Analyses of seizure responses supportive of a novel trial design to assess efficacy of antiepileptic drugs in infants and young children with epilepsy: Post hoc analyses of pediatric levetiracetam and lacosamide trials. Epilepsia Open. 2021 Jun;6(2):359-368. doi: 10.1002/epi4.12482. Epub 2021 May 3.

Reference Type: DERIVED

PMID: 34033237 (View on PubMed)

Babar RK, Bresnahan R, Gillespie CS, Michael BD. Lacosamide add-on therapy for focal epilepsy. Cochrane Database Syst Rev. 2021 May 17;5(5):CD008841. doi: 10.1002/14651858.CD008841.pub3.

Reference Type: DERIVED

PMID: 33998660 (View on PubMed)

Farkas V, Steinborn B, Flamini JR, Zhang Y, Yuen N, Borghs S, Bozorg A, Daniels T, Martin P, Carney HC, Dimova S, Scheffer IE; SP0969 Study Group. Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures. Neurology. 2019 Sep 17;93(12):e1212-e1226. doi: 10.1212/WNL.0000000000008126. Epub 2019 Aug 28.

Reference Type: DERIVED

PMID: 31462582 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

2012-004996-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SP0969

Identifier Type: -

Identifier Source: org_study_id