Clinical trial NCT02477839: Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years 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 >=1 Month to <4 Years of Age With Partial-Onset Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy With Partial-onset Seizures
Keywords: Epilepsy
children
partial-onset seizures
lacosamide
LCM
pediatric
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 255
Sex: ALL
Minimum age (years): 1
Maximum age (years): 47
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to assess the efficacy, safety and tolerability of lacosamide administered as add-on therapy with 1 to 3 anti-seizure medications. This trial is for children aged 1 month to less than 4 years with epilepsy who currently have uncontrolled partial-onset seizures.

Detailed description: The trial consists of a 7-day Baseline Period, a 20-day Titration Period, a 7-day Maintenance Period, and a 12-day Transition Period for subjects who complete the study and choose to enter the extension study. Subjects who will not enter the extension study will continue after the Maintenance Period with a 16-day Taper Period followed by a 30-day Safety Follow-Up Period. The Taper Period and Safety Follow-Up are also applicable for subjects not eligible for continuation and therefore ending the study earlier.

If subjects meet the eligibility criteria, they will be randomized to receive either lacosamide 8 mg/kg/day to 12 mg/kg/day, or placebo during the Maintenance Phase. The dose of lacosamide will be titrated from 4 mg/kg/day at study start to maximum of 12 mg/kg/day at 4-day intervals of 1-2 mg/kg/day.

All subjects who complete the 20-day Titration Period will enter the 7-day Maintenance Period. No dose adjustment is allowed during the Maintenance Phase. The Treatment Phase is defined as the combined Titration and Maintenance Phases.

Eligibility criteria: Inclusion Criteria:

* Subject is male or female from \>=1 month (ie, 4 weeks after full term \[37 weeks gestational age\]) to \<4 years of age
* Subject has a diagnosis of epilepsy with partial-onset seizures. The results of \>=1 prior EEG and \>=1 magnetic resonance imaging/computerized tomography scan should be consistent with this diagnosis
* Subject weighs \>=4 kg to \<30 kg at Visit 1
* Subject has experienced \>=2 partial-onset seizures with or without secondary generalization during each consecutive 7-day period during the 2 weeks prior to Visit 1
* Subject has \>=2 partial-onset seizures with or without secondary generalization during the End-of-Baseline video-EEG. Electrographic seizures are defined as recognizable ictal patterns on an EEG involving \>=2 contiguous electrodes. The seizures are initiated as a unilateral or strongly asymmetric abnormal epileptiform discharge lasting a total of \>10 seconds
* Subject is on a stable (concurrently or sequentially) dosage regimen of 1 to 3 AEDs. The dosage regimen of concomitant AED therapy must be kept constant for a period of \>=2 weeks prior to Visit 1. A stable daily dosage regimen of a concomitant benzodiazepine (BZD) will be considered as a concomitant AED
* Vagus nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED. The VNS device must have been implanted for \>=6 months prior to Visit 1; device settings must be kept stable for \>=2 weeks prior to Visit 1 and kept stable during the Baseline, Treatment, and Transition Periods. Use of the VNS device magnet is allowed
* Subject is an acceptable candidate for venipuncture

Exclusion Criteria:

* Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in addition to partial-onset seizures is not exclusionary
* Subject is on a ketogenic diet that has either changed within the 4 weeks prior to Visit 1 or is expected to change during the study
* Subject has creatinine clearance \<30 mL/minute
* 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 \[QTc\] \>=450 ms)
* Subject has a hemodynamically significant congenital heart disease
* Subject has an arrhythmic heart condition requiring medical therapy
* Subject has a known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias
* Subject has nonepileptic events that could be confused with seizures. Subjects may be included if epileptic events can be clearly distinguished and the frequency meets the study inclusion criteria
* Subject has a current diagnosis of Lennox-Gastaut syndrome, epilepsia partialis continua, primary generalized epilepsy, Dravet Syndrome, or seizures that are not of partial-onset origin
* Subject has a history of generalized convulsive status epilepticus \<=2 months prior to Screening (Visit 1)
* 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. Subjects treated with felbamate for \>=12 months prior to Visit 1 and who have not experienced serious toxicity issues are eligible
* Subject has an acute or subacutely 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)
* Subject has a known cardiac sodium channelopathy, such as Brugada syndrome

Primary outcomes:
measure: Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Participant Withdrawals Due to Adverse Events (AEs) During the Study
timeFrame: From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)
measure: Percentage of Participants With Adverse Events Reported Spontaneously by the Participant's Parent(s) and/or Legal Representative(s)/Caregiver(s) (in Accordance With Local Regulation) or Observed by the Investigator
timeFrame: From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)
Secondary outcomes:
measure: Absolute Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Percent Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Who Achieved 'Seizure-free' Status From All Seizure Types During the End-of-Maintenance (EOM) Period Video-EEG
timeFrame: During the End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Who Achieved 'Seizure-free' Status From Partial-onset Seizure Types Only During the End-of-Maintenance (EOM) Period Video-EEG
timeFrame: During the End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Experiencing a >=25% to <50% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Experiencing a 50% to 75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Experiencing a >75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Experiencing no Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures (Between <25% Reduction and <25% Increase) From EOB Period Video-EEG to EOM Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
measure: Percentage of Participants Experiencing an Increase in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures of >=25% From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
timeFrame: End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Sp0967 638
state: Alabama
city: Tampa
country: United States
facility: Sp0967 117
state: Florida
city: Henderson
country: United States
facility: Sp0967 115
state: Nevada
city: Lebanon
country: United States
facility: Sp0967 120
state: New Hampshire
city: Dallas
country: United States
facility: Sp0967 129
state: Texas
city: San Antonio
country: United States
facility: Sp0967 630
state: Texas
city: San Antonio
country: United States
facility: Sp0967 643
state: Texas
city: Córdoba
country: Argentina
facility: Sp0967 142
city: Passo Fundo
country: Brazil
facility: Sp0967 158
city: Porto Alegre
country: Brazil
facility: Sp0967 152
city: São Paulo
country: Brazil
facility: Sp0967 150
city: São Paulo
country: Brazil
facility: Sp0967 154
city: Plovdiv
country: Bulgaria
facility: Sp0967 310
city: Beijing
country: China
facility: Sp0967 530
city: Changchun
country: China
facility: Sp0967 535
city: Chongqing
country: China
facility: Sp0967 532
city: Nanchang
country: China
facility: Sp0967 536
city: Shanghai
country: China
facility: Sp0967 531
city: Shenzhen
country: China
facility: Sp0967 537
city: Osijek
country: Croatia
facility: Sp0967 613
city: Rijeka
country: Croatia
facility: Sp0967 610
city: Zagreb
country: Croatia
facility: Sp0967 612
city: Ostrava-Poruba
country: Czechia
facility: Sp0967 320
city: Marseille
country: France
facility: Sp0967 349
city: Rennes
country: France
facility: Sp0967 346
city: Strasbourg
country: France
facility: Sp0967 344
city: Tbilisi
country: Georgia
facility: Sp0967 620
city: Tbilisi
country: Georgia
facility: Sp0967 621
city: Tbilisi
country: Georgia
facility: Sp0967 622
city: Tbilisi
country: Georgia
facility: Sp0967 623
city: Athens
country: Greece
facility: Sp0967 542
city: Budapest
country: Hungary
facility: Sp0967 361
city: Budapest
country: Hungary
facility: Sp0967 362
city: Budapest
country: Hungary
facility: Sp0967 363
city: Budapest
country: Hungary
facility: Sp0967 364
city: Budapest
country: Hungary
facility: Sp0967 368
city: Petah tikva
country: Israel
facility: Sp0967 374
city: Genova
country: Italy
facility: Sp0967 397
city: Messina
country: Italy
facility: Sp0967 398
city: Milano
country: Italy
facility: Sp0967 381
city: Napoli
country: Italy
facility: Sp0967 700
city: Roma
country: Italy
facility: Sp0967 383
city: Roma
country: Italy
facility: Sp0967 395
city: Seoul
country: Korea, Republic of
facility: Sp0967 212
city: Seoul
country: Korea, Republic of
facility: Sp0967 215
city: Aguascalientes
country: Mexico
facility: Sp0967 694
city: Chihuahua
country: Mexico
facility: Sp0967 561
city: Culiacán
country: Mexico
facility: Sp0967 569
city: Culiacán
country: Mexico
facility: Sp0967 693
city: Guadalajara
country: Mexico
facility: Sp0967 563
city: Mexico
country: Mexico
facility: Sp0967 564
city: Monterrey
country: Mexico
facility: Sp0967 568
city: Monterrey
country: Mexico
facility: Sp0967 692
city: Chisinau
country: Moldova, Republic of
facility: Sp0967 650
city: Cebu
country: Philippines
facility: Sp0967 720
city: Cebu
country: Philippines
facility: Sp0967 724
city: Manila
country: Philippines
facility: Sp0967 721
city: Manila
country: Philippines
facility: Sp0967 723
city: Quezon City
country: Philippines
facility: Sp0967 727
city: Kraków
country: Poland
facility: Sp0967 422
city: Lisbon
country: Portugal
facility: Sp0967 750
city: Bucuresti
country: Romania
facility: Sp0967 581
city: Iaşi
country: Romania
facility: Sp0967 582
city: Sibiu
country: Romania
facility: Sp0967 573
city: Timişoara
country: Romania
facility: Sp0967 577
city: Kemerovo
country: Russian Federation
facility: Sp0967 454
city: Nizhny Novgorod
country: Russian Federation
facility: Sp0967 456
city: Novosibirsk
country: Russian Federation
facility: Sp0967 452
city: Omsk
country: Russian Federation
facility: Sp0967 453
city: Perm
country: Russian Federation
facility: Sp0967 455
city: Smolensk
country: Russian Federation
facility: Sp0967 730
city: Tomsk
country: Russian Federation
facility: Sp0967 458
city: Ulyanovsk
country: Russian Federation
facility: Sp0967 459
city: Yekaterinburg
country: Russian Federation
facility: Sp0967 450
city: Belgrade
country: Serbia
facility: Sp0967 461
city: Belgrade
country: Serbia
facility: Sp0967 464
city: Novi Sad
country: Serbia
facility: Sp0967 463
city: Bratislava
country: Slovakia
facility: Sp0967 474
city: Taipei
country: Taiwan
facility: Sp0967 224
city: Bangkok
country: Thailand
facility: Sp0967 237
city: Pathum Wan
country: Thailand
facility: Sp0967 235
city: Dnipropetrovs'k
country: Ukraine
facility: Sp0967 602
city: Dnipro
country: Ukraine
facility: Sp0967 609
city: Ivano-Frankivs'k
country: Ukraine
facility: Sp0967 681
city: Kiev
country: Ukraine
facility: Sp0967 600
city: Kiev
country: Ukraine
facility: Sp0967 606
city: Uzhgorod
country: Ukraine
facility: Sp0967 682
city: Vinnytsia
country: Ukraine
facility: Sp0967 603
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: