Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02477839
Recruitment Status : Completed
First Posted : June 23, 2015
Last Update Posted : November 30, 2020
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )

Tracking Information
First Submitted Date  ICMJE May 13, 2015
First Posted Date  ICMJE June 23, 2015
Last Update Posted Date November 30, 2020
Actual Study Start Date  ICMJE June 5, 2015
Actual Primary Completion Date May 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2018)
  • Applicable for the US only if dropout rate is <=10%: The change in average daily frequency (ADF) of electrographic partial-onset seizures [ Time Frame: End-of-Baseline Perio to End-of-Maintenance Period ]
    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
  • Applicable for the EU and for the US if dropout rate is >10%: Proportion of responders: >= 50% reduction in partial onset seizure frequency from Baseline to the Maintenance Period [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    The proportion of responders where a responder is a subject experiencing a 50% or greater reduction in their average daily frequency of electrographic partial-onset seizures recorded on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG
  • Subject withdrawals due to Adverse Events (AEs) during the study [ Time Frame: From the Titration Period (day 1) to the End of Study Visit (up to 93 days) ]
  • Incidence of Adverse events reported spontaneously by the subject's parent(s) and/or legal representative(s)/caregiver(s) (in accordance with local regulation) or observed by the investigator [ Time Frame: Baseline Period to End-of-Maintenance Period ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 22, 2015)
  • Applicable for US only: The change in average daily frequency (ADF) of electrographic partial-onset seizures from Baseline to the End-of-Maintenance Period [ Time Frame: From Baseline to Day 27 (End-of-Maintenance) ]
    The change in ADF of electrographic partial-onset seizures as measured on the 72-hour End-of-Maintenance Period video-EEG (video-electroencephalogram) compared to the 72-hour End-of-Baseline Period video-EEG
  • Applicable for European Union (EU) and for US if dropout rate is >10% : Proportion of responders : ≥ 50% reduction in partial onset seizure frequency from Baseline to the End-of-Maintenance Period [ Time Frame: From Baseline to Day 27 (End-of-Maintenance) ]
    The proportion of responders where a responder is a subject experiencing a 50% or greater reduction in their average daily frequency of electrographic partial-onset seizures recorded on the 72-hour End-of-Maintenance Period video-EEG compared to the 72-hour End-of-Baseline Period video-EEG
  • Subject withdrawals due to Adverse Events (AEs) during the study [ Time Frame: From Day 1 to up to Day 93 ]
    Subject withdrawals due to AEs during the duration of Study (including up to 30 days follow up after IMP(investigational medicinal product) discontinuation)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2018)
  • Absolute change in average daily frequency (ADF) of electrographic partial-onset seizures [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    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
  • Percent change in average daily frequency (ADF) of electrographic partial-onset seizures [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    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
  • Proportion of subjects who achieved "seizure-free" status from all seizure types [ Time Frame: During the End-of-Maintenance Period ]
    Proportion of subjects who achieved "seizure-free" status (yes/no) from all seizure types for subjects who completed at least 48 hours of interpretable video-EEG recording during the End-of-Maintenance Period video-EEG
  • Proportion of subjects who achieved "seizure-free" status from partial-onset seizure types only [ Time Frame: During the End-of-Maintenance Period ]
    Proportion of subjects who achieved "seizure-free" status (yes/no) from partial-onset seizure types only for subjects who completed at least 48 hours of interpretable video-EEG recording during the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing a >=25% to <50% reduction in average daily frequency (ADF) of electrographic partial-onset seizures [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    Proportion of subjects experiencing a >=25% to <50% reduction in ADF of electrographic partial-onset seizures from the end-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing a 50% to 75% reduction in average daily frequency (ADF) of electrographic partial-onset seizures [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    Proportion of subjects experiencing 50% to 75% reduction in ADF of electrographic partial-onset seizures from the end-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing a >75% reduction in average daily frequency (ADF) of electrographic partial-onset seizures [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    Proportion of subjects experiencing a >75% reduction in ADF of electrographic partial-onset seizures from the end-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing no change in average daily frequency (ADF) of electrographic partial-onset seizures (between <25% reduction and <25% increase) [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    Proportion of subjects experiencing no change in ADF of electrographic partial-onset seizures (between <25% reduction and <25% increase) from the End-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing an increase in average daily frequency (ADF) of electrographic partial-onset seizures of >=25% [ Time Frame: End-of-Baseline Period to End-of-Maintenance Period ]
    Proportion of subjects experiencing an increase in ADF of electrographic partial-onset seizures of >=25% from the End-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
Original Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2015)
  • Absolute change in average daily frequency (ADF) of electrographic partial-onset seizures from Baseline to End-of-Maintenance [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    The absolute change in ADF of electrographic partial-onset seizures as measured on the 72-hour End-of-Maintenance Period video-EEG compared to the 72-hour End-of-Baseline Period video-EEG
  • Percent change in average daily frequency (ADF) of electrographic partial-onset seizures from Baseline to End-of Maintenance [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    The percent change in ADF of electrographic partial-onset seizures as measured on the 72-hour End-of-Maintenance Period video-EEG compared to the 72-hour End-of-Baseline Period video-EEG
  • Proportion of subjects who achieved "seizure-free" status at the End-of-Maintenance Period [ Time Frame: At Day 27 (End-of-Maintenance Period) ]
    Proportion of subjects who achieved "seizure-free" status (yes/no) for subjects who completed at least 48 hours of interpretable video-EEG recording during the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing a ≥ 25% to < 50% reduction in average daily frequency (ADF) of electrographic partial-onset seizures from Baseline to the End-of-Maintenance Period [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    Proportion of subjects experiencing a ≥ 25% to < 50% reduction in ADF of electrographic partial-onset seizures from the End-Of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing a 50% to 75% reduction in average daily frequency (ADF) of electrographic partial-onset seizures from Baseline to the End-of-Maintenance Period [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    Proportion of subjects experiencing 50% to 75% reduction in ADF of electrographic partial-onset seizures from the end-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing no change in average daily frequency (ADF) of electrographic partial-onset seizures (between <25% reduction and <25% increase) from Baseline to the End-of-Maintenance Period [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    Proportion of subjects experiencing no change in ADF of electrographic partial-onset seizures (between <25% reduction and <25% increase) from the End-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing a >75% reduction in average daily frequency (ADF) of electrographic partial-onset seizures from Baseline to the End-of Maintenance [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    Proportion of subjects experiencing a >75% reduction in ADF of electrographic partial-onset seizures from the end-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
  • Proportion of subjects experiencing an increase in average daily frequency (ADF) of electrographic partial-onset seizures of ≥25% from Baseline to the End-of-Maintenance Period [ Time Frame: Baseline to Day 27 (End-of-Maintenance) ]
    Proportion of subjects experiencing an increase in ADF of electrographic partial-onset seizures of ≥25% from the End-of-Baseline Period video-EEG to the End-of-Maintenance Period video-EEG
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures
Official Title  ICMJE 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
Brief Summary The purpose of this trial is to assess the efficacy, safety and tolerabilty 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy With Partial-onset Seizures
Intervention  ICMJE
  • Drug: Lacosamide
    Active Substance: Lacosamide Pharmaceutical Form: Syrup Concentration: 10 mg/mL Route of Administration: oral
    Other Names:
    • Vimpat
    • UCB Code: SPM 927
    • Abreviated name: LCM
  • Other: Placebo
    Active Substance: Placebo Pharmaceutical Form: Syrup Concentration: N/A Route of Administration: oral
    Other Name: PBO
Study Arms  ICMJE
  • Experimental: Lacosamide
    Lacosamide syrup 8 mg/kg/day to 12 mg/kg/day
    Intervention: Drug: Lacosamide
  • Placebo Comparator: Placebo
    Matching placebo syrup
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 11, 2020)
255
Original Estimated Enrollment  ICMJE
 (submitted: June 22, 2015)
244
Actual Study Completion Date  ICMJE May 28, 2020
Actual Primary Completion Date May 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Syndorme, 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 47 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Bulgaria,   China,   Croatia,   Czechia,   France,   Georgia,   Greece,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Moldova, Republic of,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Slovakia,   Taiwan,   Thailand,   Ukraine,   United States
Removed Location Countries Australia,   Belgium,   Chile,   Colombia,   Czech Republic,   Finland,   Germany,   Lithuania,   Spain,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT02477839
Other Study ID Numbers  ICMJE SP0967
2013-000717-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UCB Pharma ( UCB BIOSCIENCES, Inc. )
Study Sponsor  ICMJE UCB BIOSCIENCES, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: UCB Cares +1 877 822 9493 (UCB)
PRS Account UCB Pharma
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP