An Open-Label Study to Determine Safety , Tolerability, and Efficacy of Oral Lacosamide in Children With Epilepsy

An Open-Label Study To Determine Safety, Tolerability And Efficacy Of Long -Term Oral Lacosamide (LCM) As Adjunctive Therapy In Children With Epilepsy

SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Lacosamide; Drug: Lacosamide

Detailed Description

SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy. In addition, the study is designed to provide continued availability of LCM to subjects who have completed the SP847 (NCT00938431) study and to subjects who have discontinued from SP847 (NCT00938431) and who, in the investigator's opinion, would benefit from long-term administration of LCM.

SP848 will be open to subjects who have participated in other LCM pediatric clinical studies in epilepsy and will also be open to up to 100 subjects enrolling directly into SP848. Permissible LCM doses in SP848 are between 2-12 mg/kg/day (oral solution [syrup]) or the corresponding tablet dose up to a maximum dose of 600 mg/day.

Subjects enrolled in SP848 have the option of remaining on the oral solution formulation of LCM or switching to the commercial tablet formulation, if feasible.

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 2

Expanded Access

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

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Sp848 201
  • Edegem, Belgium
    • Sp848 200
  • Gent, Belgium
    • Sp848 203
  • Leuven, Belgium
    • Sp848 202
• China
  • Beijing, China
    • Sp848 950
  • Chang Chun, China
    • Sp848 953
  • Chongqing, China
    • Sp848 951
  • Hanzhou, China
    • Sp848 955
  • Nanchang, China
    • Sp848 956
  • Shanghai, China
    • Sp848 952
  • Shenzhen, China
    • Sp848 954
• France
  • Paris, France
    • Sp848 309
  • Strasbourg Cedex, France
    • Sp848 304
• Germany
  • Kork, Germany
    • Sp848 403
• Hungary
  • Budapest, Hungary
    • Sp848 701
  • Budapest, Hungary
    • Sp848 702
  • Budapest, Hungary
    • Sp848 703
  • Budapest, Hungary
    • Sp848 704
  • Debrecen, Hungary
    • Sp848 705
• Italy
  • Messina, Italy
    • Sp848 503
  • Verona, Italy
    • Sp848 502
• Japan
  • Fukuoka, Japan
    • Sp848 257
  • Hamamatsu, Japan
    • Sp848 256
  • Kodaira, Japan
    • Sp848 255
  • Koshi, Japan
    • Sp848 253
  • Niigata, Japan
    • Sp848 252
  • Okayama, Japan
    • Sp848 258
  • Osaka, Japan
    • Sp848 254
  • Osaka, Japan
    • Sp848 259
  • Shizuoka, Japan
    • Sp848 251
• Mexico
  • Culiacan, Mexico
    • Sp848 101
  • Guadalajara, Mexico
    • Sp848 104
  • San Luis Potosi, Mexico
    • Sp848 103
• Poland
  • Bialystok, Poland
    • Sp848 803
  • Katowice, Poland
    • Sp848 807
  • Kielce, Poland
    • Sp848 804
  • Krakow, Poland
    • Sp848 801
  • Lublin, Poland
    • Sp848 805
• Ukraine
  • Dnipropetrovs'k, Ukraine
    • Sp848 224
  • Dnipropetrovs'k, Ukraine
    • Sp848 225
  • Ivano-Frankivs'k, Ukraine
    • Sp848 220
  • Kiev, Ukraine
    • Sp848 221
  • Kiev, Ukraine
    • Sp848 222
  • Kiev, Ukraine
    • Sp848 226
  • Vinnytsia, Ukraine
    • Sp848 223
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Sp848 064
  • California
    • Los Angeles, California, United States, 90027-6062
      • Sp848 059
    • Sacramento, California, United States, 95815
      • Sp848 025
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Sp848 002
  • Florida
    • Orlando, Florida, United States, 32819
      • Sp848 054
    • Tampa, Florida, United States, 33609
      • Sp848 012
    • Wellington, Florida, United States, 33470
      • Sp848 019
  • Georgia
    • Augusta, Georgia, United States, 30912-4005
      • Sp848 057
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Sp848 063
    • Saint Paul, Minnesota, United States, 55102
      • Sp848 006
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Sp848 008
  • Nevada
    • Las Vegas, Nevada, United States, 89052
      • Sp848 061
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Sp848 062
    • New Brunswick, New Jersey, United States, 08901
      • Sp848 015
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Sp848 005
  • Ohio
    • Akron, Ohio, United States, 44308
      • Sp848 053
    • Cincinnati, Ohio, United States, 45229
      • Sp848 068
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Sp848 001
    • Pittsburgh, Pennsylvania, United States, 15201
      • Sp848 016
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Sp848 004
  • Texas
    • Austin, Texas, United States, 78723
      • Sp848 026
    • Dallas, Texas, United States, 75235
      • Sp848 067
    • Houston, Texas, United States, 77076
      • Sp848 022
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Sp848 020

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A signed informed consent form has been obtained from the parent/legal guardian and assent has been obtained from the subject, as required
• Subject and caregiver (which may be a parent, legal guardian, or other delegated caregiver) are willing and able to comply with all study requirements, including maintaining a daily seizure diary

Subjects who have participated in SP847 or other lacosamide (LCM) pediatric clinical studies in epilepsy must fulfill the following inclusion criteria:

• Subject has completed SP847 (or the subject discontinued SP847 due to a dose reduction or status epilepticus) for the treatment of uncontrolled partial-onset seizures, or subject has participated in other LCM pediatric clinical studies in epilepsy
• Subject is expected to benefit from participation, in the opinion of the investigator

Subjects who enroll directly into SP848 without previous participation in a LCM clinical study must fulfill the following inclusion criteria:

• Subject is >=4 years to <=17 years of age
• Subject has a diagnosis of epilepsy with partial-onset seizures
• Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with at least 2 Antiepileptic Drugs (AEDs) (concurrently or sequentially)
• Subject has been observed to have at least 2 countable seizures in the 4 week period prior to Screening
• Subject is on a stable dosage regimen of 1 to 3 AEDs
• Subject is an acceptable candidate for venipuncture

Exclusion Criteria:

• Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)
• Subject >= 6 years of age has a lifetime history of suicide attempt, or has suicidal ideation in the past 6 months

Subjects who have participated in SP847 or other LCM pediatric clinical studies in epilepsy are not permitted to enroll in the study if any of the following criteria are met:

• Subject meets either of the following:

  1. Withdrawal criteria for the primary study (with the exception of subjects who discontinued due to a dose reduction or status epilepticus). For subjects entering from EP0060, if the subject (or legal guardian) withdraws consent solely due to route of LCM administration (iv) or if the subject requires more than 10 iv LCM infusions, the subject may be allowed to participant in SP848 after discussion with and agreement from the Medical Monitor

  2. Ongoing serious Adverse Event (SAE)

     Subjects who enroll directly into SP848 without previous participation in a LCM clinical study are not permitted to enroll in the study if any of the following criteria are met:

• Subject has ever received LCM
• 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 has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion
• Subject has a known hypersensitivity to any component of the investigational medicinal product
• Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of the study
• Subject has a creatinine clearance less than 30mL/min
• Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450ms)
• Subject has hemodynamically significant heart disease (eg, heart failure)
• 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, including psychogenic seizures, that could be confused with seizures. If both epileptic and nonepileptic events are present, epileptic events must be distinguished from nonepileptic phenomena
• Subject has a history of primary generalized epilepsy
• Subject is taking monoamine oxidase inhibitors-A (MAOI-A) or narcotic analgesics.
• Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen syndrome
• Subject has a known sodium channelopathy, such as Brugada syndrome
• Subject has >2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35%)

Subjects who were directly enrolled in EP0060 for iv LCM replacement therapy or to initiate LCM treatment are not permitted to enroll in the study if any of the following criteria are met:

- Subjects have previously participated in a long-term, open-label LCM study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacosamide; Subjects and their caregivers may chose to receive Lacosamide oral solution (syrup) or Lacosamide tablets. The maximum duration of LCM administration will be approximately 2 years.	Drug: Lacosamide; Lacosamide oral solution (syrup): Total daily dose between 2 mg/kg/day (1 mg/kg bid) to 12 mg/kg/day (6 mg/kg bid); Other Names: Vimpat®; Drug: Lacosamide; Lacosamide tablets: Total daily dose between 100 mg (50mg bid) - 600mg (300 mg bid). The maximum permissible dose of LCM will be 12 mg/kg/day or 600 mg/day.; Other Names: Vimpat®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)	An AE is any untoward medical occurrence in a participant or clinical investigation study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.	From Baseline to End of Safety Follow-Up (up to 4.3 years)
Number of Participants With Serious Adverse Events (SAEs)	SAE was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in participant hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment with parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above.	From Baseline to End of Safety Follow-Up (up to 4.3 years)
Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event	TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.	From Baseline to End of Safety Follow-Up (up to 4.3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period	Percent change in seizure frequency per 28 days (PCH) from the Baseline value (B) to Treatment Period interval (T) was defined as:PCH = [(SFT - SFB)/SFB] x 100 where, SFT corresponded to seizure frequency during Treatment Period for relative interval in open-label study and SFB corresponded to Baseline seizure frequency. For both periods, the frequency was standardized to the number of seizures per 28 days. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count case report form/electronic case report form (CRF/eCRF) module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060.	From Baseline to End of Treatment Period (up to 4.2 years)
Percentage of Participants With ≥50% Reduction in 28-day Partial-onset Seizure Frequency	A 50% responder is a participant experiencing a ≥50% reduction in partial-onset seizure frequency per 28 days from Baseline to end of the specified time interval, otherwise a participant is a non-responder. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count CRF/eCRF module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060.	From Baseline to End of Treatment Period (up to 4.2 years)
Percentage of Participants With ≥75% Reduction in 28-day Partial-onset Seizure Frequency	A 75% responder is a participant experiencing a ≥75% reduction in partial-onset seizure frequency per 28 days from Baseline to end of the specified time interval, otherwise a participant is a non-responder. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count CRF/eCRF module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060.	From Baseline to End of Treatment Period (up to 4.2 years)
Number of Seizure Days Per 28 Days for Participants With Generalized Seizures	A seizure day was defined as a day where any type of seizure was reported in the seizure diary and seizures were assessed. Days in the seizure diary which were marked as "not done" on the CRF/eCRF were not counted as seizure-free days.	Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96
Percentage of Participants Who Achieved a Seizure-free Status	Study participants were considered seizure-free for a given period if they completed the period, reported zero seizures during the period, and had no more than 10% of days in the period for which seizure data were not available (ie, "not done" was noted on the Seizure Frequency CRF/eCRF module).	From Baseline to End of Treatment Period (up to 4.2 years)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES, Inc.

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2009
• Primary Completion (Actual): May 18, 2021
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: July 10, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Actual): January 18, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Lacosamide (VIMPAT)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: SP848; 2011-001559-35 (EudraCT Number)