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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Drug: Lacosamide


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lacosamide, Vimpat, Children, Epilepsy, Seizures, Anti-epileptic