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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00938431
• Other study ID #: SP0847
• Secondary ID: 2011-001558-27
• Status: Completed
• Phase: Phase 2
• Start date: November 2009
• Est. completion date: August 2014

Study information

• Verified date: July 2017
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Lacosamide
Lacosamide oral solution (syrup) 10 mg/mL or 15 mg/mL

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Mexico, 

References & Publications (1)

Winkler J, Schoemaker R, Stockis A. Population Pharmacokinetics of Adjunctive Lacosamide in Pediatric Patients With Epilepsy. J Clin Pharmacol. 2018 Nov 14. doi: 10.1002/jcph.1340. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks)		13 weeks
Secondary	Change in Seizure Frequency From Baseline to End of Treatment		From Baseline to End of Treatment (approximately 13 weeks)
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: Very much improved; Much improved; Minimally improved; No change; Minimally worse; Much worse; Very much worse	Visit 5 (Day 27/28) or Early Termination
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: Very much improved; Much improved; Minimally improved; No Change; Minimally worse; Much worse; Very much worse	Visit 5 (Day 27/28) or Early Termination
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.	Day 7
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.	Day 28
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.	Day 35
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.	Day 42
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.	Day 7
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.	Day 28
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.	Day 35
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.	Day 42

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