Clinical trial NCT00938912: An Open-Label Study to Determine Safety , Tolerability, and Efficacy of Oral Lacosamide in Children With Epilepsy
Official title: An Open-Label Study To Determine Safety, Tolerability And Efficacy Of Long -Term Oral Lacosamide (LCM) As Adjunctive Therapy In Children With Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Keywords: Lacosamide (VIMPAT)
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2009-07-14
Enrollment: 366
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy.

Detailed description: SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy. In addition, the study is designed to provide continued availability of LCM to subjects who have completed the SP847 (NCT00938431) study and to subjects who have discontinued from SP847 (NCT00938431) and who, in the investigator's opinion, would benefit from long-term administration of LCM.

SP848 will be open to subjects who have participated in other LCM pediatric clinical studies in epilepsy and will also be open to up to 100 subjects enrolling directly into SP848. Permissible LCM doses in SP848 are between 2-12 mg/kg/day (oral solution \[syrup\]) or the corresponding tablet dose up to a maximum dose of 600 mg/day.

Subjects enrolled in SP848 have the option of remaining on the oral solution formulation of LCM or switching to the commercial tablet formulation, if feasible.

Eligibility criteria: Inclusion Criteria:

* A signed informed consent form has been obtained from the parent/legal guardian and assent has been obtained from the subject, as required
* Subject and caregiver (which may be a parent, legal guardian, or other delegated caregiver) are willing and able to comply with all study requirements, including maintaining a daily seizure diary

Subjects who have participated in SP847 or other lacosamide (LCM) pediatric clinical studies in epilepsy must fulfill the following inclusion criteria:

* Subject has completed SP847 (or the subject discontinued SP847 due to a dose reduction or status epilepticus) for the treatment of uncontrolled partial-onset seizures, or subject has participated in other LCM pediatric clinical studies in epilepsy
* Subject is expected to benefit from participation, in the opinion of the investigator

Subjects who enroll directly into SP848 without previous participation in a LCM clinical study must fulfill the following inclusion criteria:

* Subject is \>=4 years to \<=17 years of age
* 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 (in the opinion of the investigator) with at least 2 Antiepileptic 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
* Subject is an acceptable candidate for venipuncture

Exclusion Criteria:

* Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)
* Subject \>= 6 years of age has a lifetime history of suicide attempt, or has suicidal ideation in the past 6 months

Subjects who have participated in SP847 or other LCM pediatric clinical studies in epilepsy are not permitted to enroll in the study if any of the following criteria are met:

* Subject meets either of the following:

  1. Withdrawal criteria for the primary study (with the exception of subjects who discontinued due to a dose reduction or status epilepticus). For subjects entering from EP0060, if the subject (or legal guardian) withdraws consent solely due to route of LCM administration (iv) or if the subject requires more than 10 iv LCM infusions, the subject may be allowed to participant in SP848 after discussion with and agreement from the Medical Monitor
  2. Ongoing serious Adverse Event (SAE)

     Subjects who enroll directly into SP848 without previous participation in a LCM clinical study are not permitted to enroll in the study if any of the following criteria are met:
* Subject has ever received LCM
* Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study.
* Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion
* Subject has a known hypersensitivity to any component of the investigational medicinal product
* Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of the study
* Subject has a creatinine clearance less than 30mL/min
* Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450ms)
* Subject has hemodynamically significant heart disease (eg, heart failure)
* Subject has an arrhythmic heart condition requiring medical therapy
* Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias
* Subject has nonepileptic events, including psychogenic seizures, that could be confused with seizures. If both epileptic and nonepileptic events are present, epileptic events must be distinguished from nonepileptic phenomena
* Subject has a history of primary generalized epilepsy
* Subject is taking monoamine oxidase inhibitors-A (MAOI-A) or narcotic analgesics.
* Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen syndrome
* Subject has a known sodium channelopathy, such as Brugada syndrome
* Subject has \>2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or \>ULN total bilirubin (1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are \>ULN and \<1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin \<35%)

Subjects who were directly enrolled in EP0060 for iv LCM replacement therapy or to initiate LCM treatment are not permitted to enroll in the study if any of the following criteria are met:

- Subjects have previously participated in a long-term, open-label LCM study

Primary outcomes:
measure: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: From Baseline to End of Safety Follow-Up (up to 4.3 years)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Baseline to End of Safety Follow-Up (up to 4.3 years)
measure: Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event
timeFrame: From Baseline to End of Safety Follow-Up (up to 4.3 years)
Secondary outcomes:
measure: Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period
timeFrame: From Baseline to End of Treatment Period (up to 4.2 years)
measure: Percentage of Participants With ≥50% Reduction in 28-day Partial-onset Seizure Frequency
timeFrame: From Baseline to End of Treatment Period (up to 4.2 years)
measure: Percentage of Participants With ≥75% Reduction in 28-day Partial-onset Seizure Frequency
timeFrame: From Baseline to End of Treatment Period (up to 4.2 years)
measure: Number of Seizure Days Per 28 Days for Participants With Generalized Seizures
timeFrame: Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96
measure: Percentage of Participants Who Achieved a Seizure-free Status
timeFrame: From Baseline to End of Treatment Period (up to 4.2 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Sp848 064
state: Alabama
city: Los Angeles
country: United States
facility: Sp848 059
state: California
city: Sacramento
country: United States
facility: Sp848 025
state: California
city: Washington
country: United States
facility: Sp848 002
state: District of Columbia
city: Orlando
country: United States
facility: Sp848 054
state: Florida
city: Tampa
country: United States
facility: Sp848 012
state: Florida
city: Wellington
country: United States
facility: Sp848 019
state: Florida
city: Augusta
country: United States
facility: Sp848 057
state: Georgia
city: Saint Paul
country: United States
facility: Sp848 063
state: Minnesota
city: Saint Paul
country: United States
facility: Sp848 006
state: Minnesota
city: Kansas City
country: United States
facility: Sp848 008
state: Missouri
city: Las Vegas
country: United States
facility: Sp848 061
state: Nevada
city: Hackensack
country: United States
facility: Sp848 062
state: New Jersey
city: New Brunswick
country: United States
facility: Sp848 015
state: New Jersey
city: Durham
country: United States
facility: Sp848 005
state: North Carolina
city: Akron
country: United States
facility: Sp848 053
state: Ohio
city: Cincinnati
country: United States
facility: Sp848 068
state: Ohio
city: Philadelphia
country: United States
facility: Sp848 001
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Sp848 016
state: Pennsylvania
city: Nashville
country: United States
facility: Sp848 004
state: Tennessee
city: Austin
country: United States
facility: Sp848 026
state: Texas
city: Dallas
country: United States
facility: Sp848 067
state: Texas
city: Houston
country: United States
facility: Sp848 022
state: Texas
city: Norfolk
country: United States
facility: Sp848 020
state: Virginia
city: Brussels
country: Belgium
facility: Sp848 201
city: Edegem
country: Belgium
facility: Sp848 200
city: Gent
country: Belgium
facility: Sp848 203
city: Leuven
country: Belgium
facility: Sp848 202
city: Beijing
country: China
facility: Sp848 950
city: Chang Chun
country: China
facility: Sp848 953
city: Chongqing
country: China
facility: Sp848 951
city: Hanzhou
country: China
facility: Sp848 955
city: Nanchang
country: China
facility: Sp848 956
city: Shanghai
country: China
facility: Sp848 952
city: Shenzhen
country: China
facility: Sp848 954
city: Paris
country: France
facility: Sp848 309
city: Strasbourg Cedex
country: France
facility: Sp848 304
city: Kork
country: Germany
facility: Sp848 403
city: Budapest
country: Hungary
facility: Sp848 701
city: Budapest
country: Hungary
facility: Sp848 702
city: Budapest
country: Hungary
facility: Sp848 703
city: Budapest
country: Hungary
facility: Sp848 704
city: Debrecen
country: Hungary
facility: Sp848 705
city: Messina
country: Italy
facility: Sp848 503
city: Verona
country: Italy
facility: Sp848 502
city: Fukuoka
country: Japan
facility: Sp848 257
city: Hamamatsu
country: Japan
facility: Sp848 256
city: Kodaira
country: Japan
facility: Sp848 255
city: Koshi
country: Japan
facility: Sp848 253
city: Niigata
country: Japan
facility: Sp848 252
city: Okayama
country: Japan
facility: Sp848 258
city: Osaka
country: Japan
facility: Sp848 254
city: Osaka
country: Japan
facility: Sp848 259
city: Shizuoka
country: Japan
facility: Sp848 251
city: Culiacan
country: Mexico
facility: Sp848 101
city: Guadalajara
country: Mexico
facility: Sp848 104
city: San Luis Potosi
country: Mexico
facility: Sp848 103
city: Bialystok
country: Poland
facility: Sp848 803
city: Katowice
country: Poland
facility: Sp848 807
city: Kielce
country: Poland
facility: Sp848 804
city: Krakow
country: Poland
facility: Sp848 801
city: Lublin
country: Poland
facility: Sp848 805
city: Dnipropetrovs'k
country: Ukraine
facility: Sp848 224
city: Dnipropetrovs'k
country: Ukraine
facility: Sp848 225
city: Ivano-Frankivs'k
country: Ukraine
facility: Sp848 220
city: Kiev
country: Ukraine
facility: Sp848 221
city: Kiev
country: Ukraine
facility: Sp848 222
city: Kiev
country: Ukraine
facility: Sp848 226
city: Vinnytsia
country: Ukraine
facility: Sp848 223
Study officials:
affiliation: +1 844 599 2273(UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: