Clinical trial NCT01921205: Study to Investigate Lacosamide as Add-on Therapy in Subjects ≥4 Years to <17 Years of Age With Partial Onset Seizures
Official title: A Multicenter, Double Blind, Randomized, Placebo Controlled, Parallel Group Study to Investigate the Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects With Epilepsy ≥4 Years to <17 Years of Age With Partial Onset Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Lacosamide
Vimpat
UCB
Epilepsy
Partial Onset Seizures
Pediatric
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2013-08-13
Enrollment: 404
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period
timeFrame: Baseline to Week 16 (or last value on treatment)
Secondary outcomes:
measure: Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures
timeFrame: Baseline to Week 16 (or last value on treatment)
measure: Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period
timeFrame: Week 7 to Week 16
measure: Proportion of Subjects Who Achieved "Seizure Free" Status (Yes/no) for Subjects Who Completed the Maintenance Period
timeFrame: Week 7 to Week 16
Other outcomes:
Locations:
city: Boulder
country: United States
facility: 127
state: Colorado
city: Orlando
country: United States
facility: 105
state: Florida
city: Tampa
country: United States
facility: 117
state: Florida
city: Atlanta
country: United States
facility: 103
state: Georgia
city: Lexington
country: United States
facility: 124
state: Kentucky
city: Louisville
country: United States
facility: 112
state: Kentucky
city: Shreveport
country: United States
facility: 121
state: Louisiana
city: Las Vegas
country: United States
facility: 115
state: Nevada
city: Charlotte
country: United States
facility: 102
state: North Carolina
city: Eugene
country: United States
facility: 640
state: Oregon
city: Dallas
country: United States
facility: 122
state: Texas
city: Tomball
country: United States
facility: 101
state: Texas
city: Seattle
country: United States
facility: 114
state: Washington
city: Buenos Aires
country: Argentina
facility: 143
city: Cordoba
country: Argentina
facility: 142
city: Heidelberg West
country: Australia
facility: 200
city: Herston
country: Australia
facility: 203
city: South Brisbane
country: Australia
facility: 205
city: Brussels
country: Belgium
facility: 304
city: Sofia
country: Bulgaria
facility: 310
city: Sofia
country: Bulgaria
facility: 312
city: Floridablanca
country: Colombia
facility: 172
city: Medellin
country: Colombia
facility: 171
city: Osijek
country: Croatia
facility: 613
city: Rijeka
country: Croatia
facility: 610
city: Zagreb
country: Croatia
facility: 612
city: Hradec Kralove
country: Czechia
facility: 321
city: Ostrava-Poruba
country: Czechia
facility: 320
city: Praha 4
country: Czechia
facility: 322
city: Praha 5
country: Czechia
facility: 323
city: Tallinn
country: Estonia
facility: 331
city: Tartu
country: Estonia
facility: 330
city: Tbilisi
country: Georgia
facility: 620
city: Tbilisi
country: Georgia
facility: 621
city: Tbilisi
country: Georgia
facility: 622
city: Tbilisi
country: Georgia
facility: 623
city: Budapest
country: Hungary
facility: 361
city: Budapest
country: Hungary
facility: 362
city: Budapest
country: Hungary
facility: 363
city: Budapest
country: Hungary
facility: 364
city: Debrecen
country: Hungary
facility: 360
city: Miskolc
country: Hungary
facility: 367
city: Pecs
country: Hungary
facility: 366
city: Holon
country: Israel
facility: 370
city: Kfar Saba
country: Israel
facility: 371
city: Petach Tikva
country: Israel
facility: 374
city: Tel Aviv
country: Israel
facility: 372
city: Bologna
country: Italy
facility: 384
city: Florence
country: Italy
facility: 388
city: Genova
country: Italy
facility: 387
city: Mantova
country: Italy
facility: 380
city: Milano
country: Italy
facility: 381
city: Padova
country: Italy
facility: 393
city: Roma
country: Italy
facility: 383
city: Roma
country: Italy
facility: 392
city: Verona
country: Italy
facility: 386
city: Daegu
country: Korea, Republic of
facility: 211
city: Seoul
country: Korea, Republic of
facility: 210
city: Seoul
country: Korea, Republic of
facility: 212
city: Seoul
country: Korea, Republic of
facility: 213
city: Seoul
country: Korea, Republic of
facility: 215
city: Riga
country: Latvia
facility: 400
city: Valmiera
country: Latvia
facility: 402
city: Kaunas
country: Lithuania
facility: 411
city: Culiacan
country: Mexico
facility: 569
city: Guadalajara
country: Mexico
facility: 563
city: Monterrey
country: Mexico
facility: 568
city: Podgorica
country: Montenegro
facility: 660
city: Gdansk
country: Poland
facility: 433
city: Katowice
country: Poland
facility: 432
city: Kielce
country: Poland
facility: 420
city: Krakow
country: Poland
facility: 422
city: Krakow
country: Poland
facility: 431
city: Poznan
country: Poland
facility: 423
city: Poznan
country: Poland
facility: 425
city: Szczecin
country: Poland
facility: 421
city: Tyniec Maly
country: Poland
facility: 429
city: Warszawa
country: Poland
facility: 430
city: Wroclaw
country: Poland
facility: 428
city: Bucuresti
country: Romania
facility: 574
city: Cluj-Napoca
country: Romania
facility: 572
city: Sibiu
country: Romania
facility: 576
city: Suceava
country: Romania
facility: 580
city: Timisoara
country: Romania
facility: 570
city: Timisoara
country: Romania
facility: 577
city: Kazan
country: Russian Federation
facility: 443
city: Kazan
country: Russian Federation
facility: 444
city: Moscow
country: Russian Federation
facility: 442
city: Moscow
country: Russian Federation
facility: 449
city: Smolensk
country: Russian Federation
facility: 440
city: St. Petersburg
country: Russian Federation
facility: 441
city: St. Petersburg
country: Russian Federation
facility: 446
city: Voronezh
country: Russian Federation
facility: 447
city: Belgrade
country: Serbia
facility: 464
city: Kragujevac
country: Serbia
facility: 460
city: Novi Beograd
country: Serbia
facility: 461
city: Novi Sad
country: Serbia
facility: 462
city: Novi Sad
country: Serbia
facility: 463
city: Bardejov
country: Slovakia
facility: 470
city: Nitra
country: Slovakia
facility: 473
city: Nove Zamky
country: Slovakia
facility: 472
city: Ljubljana
country: Slovenia
facility: 670
city: Changhua
country: Taiwan
facility: 220
city: Taichung
country: Taiwan
facility: 222
city: Taipei
country: Taiwan
facility: 224
city: Bangkoknoi
country: Thailand
facility: 236
city: Bangkok
country: Thailand
facility: 232
city: Muang
country: Thailand
facility: 231
city: Muang
country: Thailand
facility: 233
city: Pathumwan
country: Thailand
facility: 235
city: Ratchathewi
country: Thailand
facility: 230
city: Dnipropetrovsk
country: Ukraine
facility: 602
city: Kiev
country: Ukraine
facility: 606
city: Uzhgorod
country: Ukraine
facility: 682
city: Vinnitsa
country: Ukraine
facility: 603
city: Birmingham
country: United Kingdom
facility: 514
city: Birmingham
country: United Kingdom
facility: 515
city: Leeds
country: United Kingdom
facility: 511
Study officials:
affiliation: +1 877 822 9493
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.