Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures

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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy With Partial-onset Seizures
• Intervention / Treatment: Drug: Lacosamide; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina
    • Sp0967 142
• Brazil
  • Passo Fundo, Brazil
    • Sp0967 158
  • Porto Alegre, Brazil
    • Sp0967 152
  • São Paulo, Brazil
    • Sp0967 150
  • São Paulo, Brazil
    • Sp0967 154
• Bulgaria
  • Plovdiv, Bulgaria
    • Sp0967 310
• China
  • Beijing, China
    • Sp0967 530
  • Changchun, China
    • Sp0967 535
  • Chongqing, China
    • Sp0967 532
  • Nanchang, China
    • Sp0967 536
  • Shanghai, China
    • Sp0967 531
  • Shenzhen, China
    • Sp0967 537
• Croatia
  • Osijek, Croatia
    • Sp0967 613
  • Rijeka, Croatia
    • Sp0967 610
  • Zagreb, Croatia
    • Sp0967 612
• Czechia
  • Ostrava-Poruba, Czechia
    • Sp0967 320
• France
  • Marseille, France
    • Sp0967 349
  • Rennes, France
    • Sp0967 346
  • Strasbourg, France
    • Sp0967 344
• Georgia
  • Tbilisi, Georgia
    • Sp0967 620
  • Tbilisi, Georgia
    • Sp0967 621
  • Tbilisi, Georgia
    • Sp0967 622
  • Tbilisi, Georgia
    • Sp0967 623
• Greece
  • Athens, Greece
    • Sp0967 542
• Hungary
  • Budapest, Hungary
    • Sp0967 361
  • Budapest, Hungary
    • Sp0967 362
  • Budapest, Hungary
    • Sp0967 363
  • Budapest, Hungary
    • Sp0967 364
  • Budapest, Hungary
    • Sp0967 368
• Israel
  • Petah tikva, Israel
    • Sp0967 374
• Italy
  • Genova, Italy
    • Sp0967 397
  • Messina, Italy
    • Sp0967 398
  • Milano, Italy
    • Sp0967 381
  • Napoli, Italy
    • Sp0967 700
  • Roma, Italy
    • Sp0967 383
  • Roma, Italy
    • Sp0967 395
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sp0967 212
  • Seoul, Korea, Republic of
    • Sp0967 215
• Mexico
  • Aguascalientes, Mexico
    • Sp0967 694
  • Chihuahua, Mexico
    • Sp0967 561
  • Culiacán, Mexico
    • Sp0967 569
  • Culiacán, Mexico
    • Sp0967 693
  • Guadalajara, Mexico
    • Sp0967 563
  • Mexico, Mexico
    • Sp0967 564
  • Monterrey, Mexico
    • Sp0967 568
  • Monterrey, Mexico
    • Sp0967 692
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Sp0967 650
• Philippines
  • Cebu, Philippines
    • Sp0967 720
  • Cebu, Philippines
    • Sp0967 724
  • Manila, Philippines
    • Sp0967 721
  • Manila, Philippines
    • Sp0967 723
  • Quezon City, Philippines
    • Sp0967 727
• Poland
  • Kraków, Poland
    • Sp0967 422
• Portugal
  • Lisbon, Portugal
    • Sp0967 750
• Romania
  • Bucuresti, Romania
    • Sp0967 581
  • Iaşi, Romania
    • Sp0967 582
  • Sibiu, Romania
    • Sp0967 573
  • Timişoara, Romania
    • Sp0967 577
• Russian Federation
  • Kemerovo, Russian Federation
    • Sp0967 454
  • Nizhny Novgorod, Russian Federation
    • Sp0967 456
  • Novosibirsk, Russian Federation
    • Sp0967 452
  • Omsk, Russian Federation
    • Sp0967 453
  • Perm, Russian Federation
    • Sp0967 455
  • Smolensk, Russian Federation
    • Sp0967 730
  • Tomsk, Russian Federation
    • Sp0967 458
  • Ulyanovsk, Russian Federation
    • Sp0967 459
  • Yekaterinburg, Russian Federation
    • Sp0967 450
• Serbia
  • Belgrade, Serbia
    • Sp0967 461
  • Belgrade, Serbia
    • Sp0967 464
  • Novi Sad, Serbia
    • Sp0967 463
• Slovakia
  • Bratislava, Slovakia
    • Sp0967 474
• Taiwan
  • Taipei, Taiwan
    • Sp0967 224
• Thailand
  • Bangkok, Thailand
    • Sp0967 237
  • Pathum Wan, Thailand
    • Sp0967 235
• Ukraine
  • Dnipro, Ukraine
    • Sp0967 609
  • Dnipropetrovs'k, Ukraine
    • Sp0967 602
  • Ivano-Frankivs'k, Ukraine
    • Sp0967 681
  • Kiev, Ukraine
    • Sp0967 600
  • Kiev, Ukraine
    • Sp0967 606
  • Uzhgorod, Ukraine
    • Sp0967 682
  • Vinnytsia, Ukraine
    • Sp0967 603
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Sp0967 638
  • Florida
    • Tampa, Florida, United States, 33609
      • Sp0967 117
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Sp0967 115
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Sp0967 120
  • Texas
    • Dallas, Texas, United States, 75235
      • Sp0967 129
    • San Antonio, Texas, United States, 78207
      • Sp0967 630
    • San Antonio, Texas, United States, 78249
      • Sp0967 643

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacosamide; Lacosamide syrup 8 mg/kg/day to 12 mg/kg/day	Drug: Lacosamide; Active Substance: Lacosamide Pharmaceutical Form: Syrup Concentration: 10 mg/mL Route of Administration: oral; Other Names: Vimpat; UCB Code: SPM 927; Abbreviated name: LCM
Placebo Comparator: Placebo; Matching placebo syrup	Other: Placebo; Active Substance: Placebo Pharmaceutical Form: Syrup Concentration: N/A Route of Administration: oral; Other Names: PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-electroencephalogram (EEG) compared to the End-of-Baseline Period video-EEG. Seizure frequency was analyzed using an analysis of covariance (ANCOVA) with terms for treatment, pooled randomized age stratum, pooled center, and Baseline seizure ADF. Seizure ADF was log transformed using the transformation of ln(X+1), where X is the seizure ADF. Baseline seizure ADF was log transformed. Least squares means were based on log-transformed data of the full ANCOVA model.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Participant Withdrawals Due to Adverse Events (AEs) During the Study	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.	From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)
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	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.	From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The absolute change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
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	The percent change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Percentage of Participants Who Achieved 'Seizure-free' Status From All Seizure Types During the End-of-Maintenance (EOM) Period Video-EEG	A study participant was considered seizure-free from all seizures if the End-of-Maintenance (EOM) Period video-EEG had zero seizures reported from all seizure types (not just partial-onset seizures (POS)).	During the End-of-Maintenance Period (Day 24 to Day 27)
Percentage of Participants Who Achieved 'Seizure-free' Status From Partial-onset Seizure Types Only During the End-of-Maintenance (EOM) Period Video-EEG	A study participant was considered seizure free from partial-onset seizures (POS) if the End-of-Maintenance (EOM) Period video-EEG had zero POS reported.	During the End-of-Maintenance Period (Day 24 to Day 27)
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	A ≥25% to <50% response was defined as ≥25% to <50% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
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	A ≥50% to ≤75% response was defined as ≥50% to ≤75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
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	A >75% response was defined as >75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
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	No change was defined as between <25% reduction and <25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
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	An increase was defined as ≥25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2015
• Primary Completion (Actual): May 28, 2020
• Study Completion (Actual): May 28, 2020

Study Registration Dates

• First Submitted: May 13, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 23, 2015

Study Record Updates

• Last Update Posted (Actual): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Epilepsy; pediatric; children; partial-onset seizures; lacosamide; LCM
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: SP0967; 2013-000717-20 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No