Epilepsy
Conditions
Keywords
Lacosamide, Vimpat, Children, Epilepsy, Seizures, Anti-epileptic
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.
Interventions
DRUGLacosamide
Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL
Sponsors
UCB Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks) | 13 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| Change in Seizure Frequency From Baseline to End of Treatment | From Baseline to End of Treatment (approximately 13 weeks) | — |
| 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. |
| 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 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. |
Countries
Belgium, Mexico, United States
Participant flow
Recruitment details
The SP0847 study began recruitment in October 2009. The study ended in July 2014 with 47 subjects enrolled into the study.
Participants by arm
| Arm | Count |
|---|---|
| >=1 Month to <4 Years (Safety Set) Subjects were classified as belonging to the age group based on their age at time of enrollment | 15 |
| >=4 Years to <12 Years (Safety Set) Subjects were classified as belonging to the age group based on their age at time of enrollment | 23 |
| >=12 Years to <=17 Years (Safety Set) Subjects were classified as belonging to the age group based on their age at time of enrollment | 9 |
| Total Title | 47 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 8 | 6 |
| Overall Study | Did not up titrate to 12 mg kg/day | 1 | 0 | 0 |
| Overall Study | Dosing compliance issue | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Reached maximum dose early | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | >=4 Years to <12 Years (Safety Set) | >=12 Years to <=17 Years (Safety Set) | Total Title | >=1 Month to <4 Years (Safety Set) |
|---|---|---|---|---|
| Age, Continuous Age (years) | 7.41 years STANDARD_DEVIATION 2.44 | 15.15 years STANDARD_DEVIATION 1.5 | 7.03 years STANDARD_DEVIATION 5.12 | 1.58 years STANDARD_DEVIATION 1.02 |
| BMI | 17.39 kg/m^2 STANDARD_DEVIATION 2.68 | 21.38 kg/m^2 STANDARD_DEVIATION 3.12 | 17.48 kg/m^2 STANDARD_DEVIATION 3.37 | 15.27 kg/m^2 STANDARD_DEVIATION 2.33 |
| Ethnicity Hispanic or Latino | 7 participants | 3 participants | 21 participants | 11 participants |
| Ethnicity Not Hispanic or Latino | 16 participants | 6 participants | 26 participants | 4 participants |
| Height | 121.81 centimeters STANDARD_DEVIATION 14.86 | 158.93 centimeters STANDARD_DEVIATION 11.43 | 115.46 centimeters STANDARD_DEVIATION 31.23 | 79.64 centimeters STANDARD_DEVIATION 11.22 |
| Racial Group Asian | 1 participants | 0 participants | 2 participants | 1 participants |
| Racial Group Black | 4 participants | 3 participants | 7 participants | 0 participants |
| Racial Group Other/ Mixed | 0 participants | 1 participants | 8 participants | 7 participants |
| Racial Group White | 18 participants | 5 participants | 30 participants | 7 participants |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 24 Participants | 10 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 23 Participants | 5 Participants |
| Weight | 26.73 kilograms STANDARD_DEVIATION 10.2 | 54.10 kilograms STANDARD_DEVIATION 10.49 | 26.60 kilograms STANDARD_DEVIATION 17.64 | 9.90 kilograms STANDARD_DEVIATION 3.31 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 15 | 16 / 23 | 7 / 9 |
| serious Total, serious adverse events | 3 / 15 | 3 / 23 | 0 / 9 |
Outcome results
Primary
Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks)
Time frame: 13 weeks
Population: The analysis consists of the Safety Set (SS), which is all subjects who signed the informed consent form and took at least 1 dose of Lacosamide (LCM) in SP0847.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks) | 14 participants |
| >=4 Years to <12 Years (Safety Set) | Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks) | 19 participants |
| >=12 Years to <=17 Years (Safety Set) | Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks) | 9 participants |
Secondary
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: 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse
Time frame: Visit 5 (Day 27/28) or Early Termination
Population: This analysis consists of the Full Analysis Set, which is all subjects from the Safety Set who have at least 1 post-Baseline seizure diary day with available data during the SP0847 study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Improved | 7 Participants |
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Miniamally Worse | 0 Participants |
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No Change | 0 Participants |
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Very Much Improved | 3 Participants |
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No data available | 1 Participants |
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Worse | 0 Participants |
| >=1 Month to <4 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Improved | 3 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No Change | 2 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Very Much Improved | 2 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Improved | 8 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Improved | 8 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Miniamally Worse | 1 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Worse | 2 Participants |
| >=4 Years to <12 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No data available | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Miniamally Worse | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Improved | 4 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No data available | 1 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Worse | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No Change | 1 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Improved | 3 Participants |
| >=12 Years to <=17 Years (Safety Set) | Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Very Much Improved | 0 Participants |
Secondary
Change in Seizure Frequency From Baseline to End of Treatment
Time frame: From Baseline to End of Treatment (approximately 13 weeks)
Population: This analysis consists of the Full Analysis Set, which is all subjects from the Safety Set who have at least 1 post-Baseline seizure diary day with available data during the SP0847 study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Change in Seizure Frequency From Baseline to End of Treatment | 18.94 percentage change | Standard Deviation 111.44 |
| >=4 Years to <12 Years (Safety Set) | Change in Seizure Frequency From Baseline to End of Treatment | 18.38 percentage change | Standard Deviation 88.16 |
| >=12 Years to <=17 Years (Safety Set) | Change in Seizure Frequency From Baseline to End of Treatment | 34.59 percentage change | Standard Deviation 92.45 |
Secondary
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: 1. Very much improved 2. Much improved 3. Minimally improved 4. No Change 5. Minimally worse 6. Much worse 7. Very much worse
Time frame: Visit 5 (Day 27/28) or Early Termination
Population: This analysis consists of the Full Analysis Set, which is all subjects from the Safety Set who have at least 1 post-Baseline seizure diary day with available data during the SP0847 study.~For one subject in the age group \>=12 years to \<=17 years no data is available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Improved | 4 Participants |
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No data available | 0 Participants |
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Worse | 0 Participants |
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No Change | 1 Participants |
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Improved | 6 Participants |
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Very Much Improved | 2 Participants |
| >=1 Month to <4 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Worse | 1 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No data available | 0 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Very Much Improved | 2 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Improved | 7 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Improved | 9 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No Change | 2 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Worse | 3 Participants |
| >=4 Years to <12 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Worse | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Very Much Improved | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Worse | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Improved | 7 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No data available | 1 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Much Worse | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | No Change | 0 Participants |
| >=12 Years to <=17 Years (Safety Set) | Clinical Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination | Minimally Improved | 1 Participants |
Secondary
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.
Time frame: Day 28
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for Lacosamide at Day 28 | 3886.0 μg/mL | Geometric Coefficient of Variation 70.2 |
Secondary
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.
Time frame: Day 35
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for Lacosamide at Day 35 | 4033.8 μg/mL | Geometric Coefficient of Variation 52.5 |
Secondary
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.
Time frame: Day 42
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for Lacosamide at Day 42 | 4169.5 μg/mL | Geometric Coefficient of Variation 73.3 |
Secondary
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.
Time frame: Day 7
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for Lacosamide at Day 7 | 839.9 μg/mL | Geometric Coefficient of Variation 64.1 |
Secondary
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.
Time frame: Day 28
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for SPM 12809 at Day 28 | 754.9 μg/mL | Geometric Coefficient of Variation 21.1 |
Secondary
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.
Time frame: Day 35
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for SPM 12809 at Day 35 | 955.1 μg/mL | Geometric Coefficient of Variation 24.7 |
Secondary
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.
Time frame: Day 42
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for SPM 12809 at Day 42 | 1725.8 μg/mL | Geometric Coefficient of Variation 39.4 |
Secondary
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.
Time frame: Day 7
Population: The analysis consists of the Safety Set, which is all subjects who signed the informed consent form and took at least 1 dose of LCM in SP0847.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| >=1 Month to <4 Years (Safety Set) | Plasma Ctrough Values for SPM 12809 at Day 7 | 258.4 μg/mL | Geometric Coefficient of Variation 44.6 |