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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT00938431
First received: July 2, 2009
Last updated: November 10, 2015
Last verified: November 2015
  Purpose
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).

Condition Intervention Phase
Epilepsy
Drug: Lacosamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Number of Subjects That Report at Least One Treatment-emergent Adverse Event During the Study (Approximately 13 Weeks) [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Seizure Frequency From Baseline to End of Treatment [ Time Frame: From Baseline to End of Treatment (approximately 13 weeks) ] [ Designated as safety issue: No ]
  • Caregiver Global Impression of Change Score at Visit 5 (Day 27/28) or Early Termination [ Time Frame: Visit 5 (Day 27/28) or Early Termination ] [ Designated as safety issue: No ]

    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 [ Time Frame: Visit 5 (Day 27/28) or Early Termination ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 35 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 42 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 35 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 42 ] [ Designated as safety issue: No ]

    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.



Enrollment: 47
Study Start Date: November 2009
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Vimpat

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.
  Eligibility

Ages Eligible for Study:   1 Month to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00938431

Locations
United States, California
025
Sacramento, California, United States
United States, District of Columbia
002
Washington, District of Columbia, United States
United States, Florida
012
Tampa, Florida, United States
019
Wellington, Florida, United States
United States, Minnesota
006
St Paul, Minnesota, United States
United States, Missouri
008
Kansas City, Missouri, United States
United States, New Jersey
015
New Brunswick, New Jersey, United States
United States, North Carolina
005
Durham, North Carolina, United States
United States, Pennsylvania
001
Philadelphia, Pennsylvania, United States
016
Pittsburgh, Pennsylvania, United States
United States, Tennessee
004
Nashville, Tennessee, United States
United States, Texas
026
Austin, Texas, United States
022
Houston, Texas, United States
United States, Virginia
020
Norfolk, Virginia, United States
Belgium
201
Brussels, Belgium
200
Edegem, Belgium
202
Leuven, Belgium
Mexico
101
Culiacan, Mexico
104
Guadalajara, Mexico
105
Monterrey, Mexico
103
San Luis Potosi, Mexico
Sponsors and Collaborators
UCB Pharma
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT00938431     History of Changes
Other Study ID Numbers: SP0847  2011-001558-27 
Study First Received: July 2, 2009
Results First Received: June 29, 2015
Last Updated: November 10, 2015
Health Authority: United States: Food and Drug Administration
Mexico: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by UCB Pharma:
Lacosamide
Vimpat
Children
Epilepsy
Seizures
Anti-epileptic

Additional relevant MeSH terms:
Lacosamide
Anticonvulsants
Central Nervous System Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 11, 2016