A Multicenter, Open-Label Study To Investigate The Safety And Pharmacokinetics Of Lacosamide In Children With Partial Seizures

A Multicenter, Open-Label Study To Investigate The Safety, Tolerability, And Pharmacokinetics Of Lacosamide (LCM) Oral Solution (Syrup) As Adjunctive Therapy In Children With Partial-Onset Seizures

The purpose of this study was to evaluate the safety and pharmacokinetics of LCM syrup in children ages from 1 month to 17 years with uncontrolled partial seizures when added to 1 to 3 other antiepileptic drugs (AEDs).

Study Overview

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

Detailed Description

Six subjects aged 5-11 (Cohort 1) were initially enrolled at the 8 mg/kg/day dose level. Upon completion of the study for these subjects, pharmacokinetic and safety data were analyzed to determine the target dose for the remaining subjects (either 8, 10 or 12 mg/kg/day). Depending on the selected target dose, four additional age-based cohorts of subjects were to be enrolled. LCM was increased 2 mg/kg/day per week until the target dose or maximum dose able to be tolerated was achieved.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Expanded Access

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

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • 201
  • Edegem, Belgium
    • 200
  • Leuven, Belgium
    • 202
• Mexico
  • Culiacan, Mexico
    • 101
  • Guadalajara, Mexico
    • 104
  • Monterrey, Mexico
    • 105
  • San Luis Potosi, Mexico
    • 103
• United States
  • California
    • Sacramento, California, United States
      • 025
  • District of Columbia
    • Washington, District of Columbia, United States
      • 002
  • Florida
    • Tampa, Florida, United States
      • 012
    • Wellington, Florida, United States
      • 019
  • Minnesota
    • Saint Paul, Minnesota, United States
      • 006
  • Missouri
    • Kansas City, Missouri, United States
      • 008
  • New Jersey
    • New Brunswick, New Jersey, United States
      • 015
  • North Carolina
    • Durham, North Carolina, United States
      • 005
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 001
    • Pittsburgh, Pennsylvania, United States
      • 016
  • Tennessee
    • Nashville, Tennessee, United States
      • 004
  • Texas
    • Austin, Texas, United States
      • 026
    • Houston, Texas, United States
      • 022
  • Virginia
    • Norfolk, Virginia, United States
      • 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:

• Subject is male or female between 1 month and 17 years of age inclusive
• Subject's Body Mass Index (BMI) is within the 5th to 95th percentile for his/her age group
• 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 with at least 2 anti-epileptic 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

Exclusion Criteria:

• Subject is currently participating or has participated within the last 2 months in any study of an investigational drug or experimental device
• Subject with seizures that are uncountable due to clustering during the 8-week period prior to study entry
• Subject is on a ketogenic or other specialized diet
• Subject has a history of primary generalized epilepsy
• Subject has a history of status epilepticus within the 6-month period prior to Screening
• Subject is receiving concomitant treatment with felbamate or has received previous felbamate therapy within the last 6 months prior to Screening
• Subject has taken or is currently taking vigabatrin
• Subject is taking monoamine oxidase (MAO) inhibitors or narcotic analgesics
• Subject has a lifetime history of suicide attempt, or has suicidal ideation in the past 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lacosamide - Age 5 - 11 years; Cohort 1 (Age 5 - 11 years); up to 8 mg/kg/day	Drug: Lacosamide; Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL; Other Names: Vimpat
EXPERIMENTAL: Lacosamide - (Age 12 - 17 years); Cohort 2 (Age 12 - 17 years); 12 mg/kg/day.	Drug: Lacosamide; Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL; Other Names: Vimpat
EXPERIMENTAL: Lacosamide (Age 2 - 4 years); Cohort 3 (Age 2 - 4 years); 12 mg/kg/day.	Drug: Lacosamide; Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL; Other Names: Vimpat
EXPERIMENTAL: Lacosamide (Age 5 - 11 years); Cohort 4 (Age 5 - 11 years); 12 mg/kg/day.	Drug: Lacosamide; Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL; Other Names: Vimpat
EXPERIMENTAL: Lacosamide (Age 1 month - < 2 years); Cohort 5 (Age 1 month to < 2 years); 12 mg/kg/day	Drug: Lacosamide; Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL; Other Names: Vimpat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks)	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Seizure Frequency From Baseline to End of Treatment		From Baseline to End of Treatment (approximately 13 weeks)
Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination	For the assessment of the Caregiver Global Impression of Change, the caregiver (including parent/legal guardian) provided his/her assessment of the subject's clinical status, compared to Baseline (Visit 1), including an evaluation of seizure frequency and intensity, the occurrence of Adverse Events (AEs), and subject's functional status. The caregiver will be asked to check the number that best describes the subject's condition over the past 4 weeks compared to Baseline: Very much improved; Much improved; Minimally improved; No change; Minimally worse; Much worse; Very much worse	Visit 5 (Day 27/28) or Early Termination
Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination	For assessment of the Clinical Global Impression of Change, the investigator provided his/her assessment of the subject's clinical status, compared to Baseline (Visit 1), including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status. The investigator will be asked to check the number that best describes the subject's condition over the past 4 weeks compared to Baseline: Very much improved; Much improved; Minimally improved; No Change; Minimally worse; Much worse; Very much worse	Visit 5 (Day 27/28) or Early Termination
Plasma Ctrough Values for Lacosamide at Day 7	During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 7
Plasma Ctrough Values for Lacosamide at Day 28	During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 28
Plasma Ctrough Values for Lacosamide at Day 35	During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 35
Plasma Ctrough Values for Lacosamide at Day 42	During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 42
Plasma Ctrough Values for SPM 12809 at Day 7	SPM 12809 is major metabolite of LCM and is known as O-desmethyl-lacosamide. During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 7
Plasma Ctrough Values for SPM 12809 at Day 28	SPM 12809 is major metabolite of LCM and is known as O-desmethyl-lacosamide. During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 28
Plasma Ctrough Values for SPM 12809 at Day 35	SPM 12809 is major metabolite of LCM and is known as O-desmethyl-lacosamide. During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 35
Plasma Ctrough Values for SPM 12809 at Day 42	SPM 12809 is major metabolite of LCM and is known as O-desmethyl-lacosamide. During SP0847, the time points for collection of blood samples for plasma concentration analysis varied per enrollment cohort. To provide a standard summary of this information, we present the mean plasma trough concentrations (Ctrough). Ctrough levels represent the lowest level of LCM that was present in the subject with measurement taken pre-dose before the next scheduled dose of LCM. The blood sample for plasma concentration schedule varied per enrollment cohort and with protocol amendments. A PK sample was not required for a subject to be in the included in the SS although all subjects did have at least one PK sample taken during SP0847. Therefore the number of subjects presented for the PK assessments is based on the subjects in the SS who attended the respective visits and had PK concentration data at the respective time point.	Day 42

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• Winkler J, Schoemaker R, Stockis A. Population Pharmacokinetics of Adjunctive Lacosamide in Pediatric Patients With Epilepsy. J Clin Pharmacol. 2019 Apr;59(4):541-547. doi: 10.1002/jcph.1340. Epub 2018 Nov 14.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: July 2, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (ESTIMATE): July 13, 2009

Study Record Updates

• Last Update Posted (ACTUAL): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Epilepsy; Children; Seizures; Anti-epileptic; Lacosamide; Vimpat
• 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: SP0847; 2011-001558-27 (EUDRACT_NUMBER)