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

Phase 2

Completed

Conditions: Epilepsy

Interventions: Drug: Lacosamide

Registration Number: NCT00938431

Lead Sponsor: UCB Pharma

Brief Summary: 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lacosamide (Age 1 month - < 2 years)	Lacosamide	Cohort 5 (Age 1 month to \< 2 years); 12 mg/kg/day
Lacosamide (Age 5 - 11 years)	Lacosamide	Cohort 4 (Age 5 - 11 years); 12 mg/kg/day.
Lacosamide - Age 5 - 11 years	Lacosamide	Cohort 1 (Age 5 - 11 years); up to 8 mg/kg/day
Lacosamide - (Age 12 - 17 years)	Lacosamide	Cohort 2 (Age 12 - 17 years); 12 mg/kg/day.
Lacosamide (Age 2 - 4 years)	Lacosamide	Cohort 3 (Age 2 - 4 years); 12 mg/kg/day.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	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: 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse
Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination	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: 1. Very much improved 2. Much improved 3. Minimally improved 4. No Change 5. Minimally worse 6. Much worse 7. Very much worse
Plasma Ctrough Values for Lacosamide at Day 7	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.
Plasma Ctrough Values for SPM 12809 at Day 42	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.
Plasma Ctrough Values for Lacosamide at Day 28	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.
Plasma Ctrough Values for Lacosamide at Day 35	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.
Plasma Ctrough Values for Lacosamide at Day 42	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.
Plasma Ctrough Values for SPM 12809 at Day 7	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.
Plasma Ctrough Values for SPM 12809 at Day 28	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.
Plasma Ctrough Values for SPM 12809 at Day 35	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.

Trial Locations

Locations (21): 012
🇺🇸
Tampa, Florida, United States
005
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Durham, North Carolina, United States
020
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Norfolk, Virginia, United States
019
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Wellington, Florida, United States
022
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Houston, Texas, United States
015
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New Brunswick, New Jersey, United States
001
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Philadelphia, Pennsylvania, United States
008
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Kansas City, Missouri, United States
200
🇧🇪
Edegem, Belgium
202
🇧🇪
Leuven, Belgium
026
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Austin, Texas, United States
006
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Saint Paul, Minnesota, United States
025
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Sacramento, California, United States
002
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Washington, District of Columbia, United States
101
🇲🇽
Culiacan, Mexico
201
🇧🇪
Brussels, Belgium
016
🇺🇸
Pittsburgh, Pennsylvania, United States
004
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Nashville, Tennessee, United States
103
🇲🇽
San Luis Potosi, Mexico
104
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Guadalajara, Mexico
105
🇲🇽
Monterrey, Mexico