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Efficacy and Tolerability of Levetiracetam Add-On Treatment in Refractory Pediatric Patients With Partial Onset Seizures

Primary Purpose

Epilepsy

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Levetiracetam
Placebo
Sponsored by
UCB Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Levetiracetam, Keppra

Eligibility Criteria

4 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • diagnosis of epilepsy with uncontrolled partial onset seizures, whether or not secondarily generalized, and the diagnosis was >= 6 months before the Selection Visit
  • epilepsy was classifiable according to the ILAE Classification
  • >= 4 partial onset seizures during the 4 weeks preceding the Selection Visit and were required to have >= 4 partial onset seizures during each 4-week interval of the Baseline Period to qualify for randomization
  • unsatisfactory current AED treatment in terms of efficacy and/or safety
  • stable AED treatment consisting of no more than two AEDs

Exclusion Criteria:

  • treatable seizure etiology
  • epilepsy secondary to a progressive cerebral disease or any other progressively neurodegenerative disease, including Rasmussen and Landau-Kleffner diseases
  • history of status epilepticus which required hospitalization during 3 months prior to the Selection Visit
  • history of or the presence of pseudo seizures
  • current diagnosis of Lennox-Gastaut syndrome

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Levetiracetam (LEV)

    Placebo

    Arm Description

    LEV dose was titrated to a level of 60 mg/kg/day. The initial dose level was 20 mg/kg/day for the first two weeks, followed by a dose level of 40 mg/kg/day for two weeks. If lower doses were well tolerated, the LEV dose was increased to a dose level of 60 mg/kg/day for the remaining 10 weeks. The dose level could be reduced to 40 mg/kg/day if the patient did not tolerate LEV at a dose level of 60 mg/kg/day.

    Subjects received Placebo matching to LEV treatment.

    Outcomes

    Primary Outcome Measures

    Partial onset seizure frequency (Type I, Type IC included) per week during the Treatment period
    Calculated as 7-day partial onset seizure frequency.

    Secondary Outcome Measures

    50% responder rate in seizure frequency per week during the Treatment Period
    Response rate is defined as percent of patients experiencing at least a 50% reduction from baseline in the seizure frequency per week during the Treatment Period.
    Percent of patients with categorized reduction from baseline in seizure frequency per week during the Treatment Period
    Categories as follows: <-25%, -25% to <25%, 25% to <50%, 50% to <75%, 75% to <100%, and 100%
    Change from baseline in the average duration of seizure free intervals
    Intervals are defined as seizure-free if no seizures are reported.
    Number of seizure free days during the Treatment Period
    A day is regarded as seizure-free if no seizures are reported.
    Absolute change from baseline in partial onset seizure frequency per week during the Treatment Period
    Absolute change from baseline in partial onset seizure frequency during the Treatment Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Absolute change from baseline in partial onset seizure frequency per week during the Titration Period
    Absolute change from baseline in partial onset seizure frequency during the Titration Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Absolute change from baseline in partial onset seizure frequency per week during the Evaluation Period
    Absolute change from baseline in partial onset seizure frequency during the Evaluation Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Percent change from baseline in partial onset seizure frequency per week during the Treatment Period
    Percent change from baseline in partial onset seizure frequency during the Treatment Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Percent change from baseline in partial onset seizure frequency per week during the Titration Period
    Percent change from baseline in partial onset seizure frequency during the Titration Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Percent change from baseline in partial onset seizure frequency per week during the Evaluation Period
    Percent change from baseline in partial onset seizure frequency during the Evaluation Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Cumulative percentage of patients who were seizure-free since the beginning of the Evaluation Period
    A subject was regarded as seizure-free if not seizures were reported since the beginning of the Evaluation Period.
    Partial onset seizure frequency per week during the Titration Period
    Calculated as 7-day partial onset seizure frequency.
    Partial onset seizure frequency per week during the Evaluation Period
    Calculated as 7-day partial onset seizure frequency.
    Total seizure frequency per week (Types I + II + III) during the Treatment Period
    Calculated as 7-day partial onset seizure frequency.
    Total seizure frequency per week (Types I + II + III) during the Titration Period
    Calculated as 7-day partial onset seizure frequency.
    Total seizure frequency per week (Types I + II + III) during the Evaluation Period
    Calculated as 7-day partial onset seizure frequency.

    Full Information

    First Posted
    January 27, 2008
    Last Updated
    July 28, 2020
    Sponsor
    UCB Pharma
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00615615
    Brief Title
    Efficacy and Tolerability of Levetiracetam Add-On Treatment in Refractory Pediatric Patients With Partial Onset Seizures
    Official Title
    Evaluation of the Efficacy and Tolerability of Levetiracetam Add-On Treatment in Refractory Pediatric Patients With Partial Onset Seizures: A 28-Week Double-Blind, Placebo-Controlled Multi-center Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    September 1999 (Actual)
    Primary Completion Date
    March 2003 (Actual)
    Study Completion Date
    March 2003 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    UCB Pharma

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Double-blind, randomized, placebo-controlled, multi-center clinical trial conducted to evaluate levetiracetam as adjunctive therapy in children (4-16 years) with refractory partial onset seizures.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Epilepsy
    Keywords
    Levetiracetam, Keppra

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    216 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Levetiracetam (LEV)
    Arm Type
    Experimental
    Arm Description
    LEV dose was titrated to a level of 60 mg/kg/day. The initial dose level was 20 mg/kg/day for the first two weeks, followed by a dose level of 40 mg/kg/day for two weeks. If lower doses were well tolerated, the LEV dose was increased to a dose level of 60 mg/kg/day for the remaining 10 weeks. The dose level could be reduced to 40 mg/kg/day if the patient did not tolerate LEV at a dose level of 60 mg/kg/day.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Subjects received Placebo matching to LEV treatment.
    Intervention Type
    Drug
    Intervention Name(s)
    Levetiracetam
    Intervention Description
    high total tablet weight (HTTW) formulation in tablet strengths of 166.5 mg, 250 mg, and 500 mg was used for patients weighing at least 40.1 kg low total tablet weight (LTTW) formulation in tablet strengths of 166 mg and 250 mg was used for patients weighing 40 kg or less
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo tablets for oral administration that were identical in appearance to the respective formulations (LTTW and HTTW) were used as reference therapy
    Primary Outcome Measure Information:
    Title
    Partial onset seizure frequency (Type I, Type IC included) per week during the Treatment period
    Description
    Calculated as 7-day partial onset seizure frequency.
    Time Frame
    During the 14-weeks Treatment period (Week 8 to Week 22)
    Secondary Outcome Measure Information:
    Title
    50% responder rate in seizure frequency per week during the Treatment Period
    Description
    Response rate is defined as percent of patients experiencing at least a 50% reduction from baseline in the seizure frequency per week during the Treatment Period.
    Time Frame
    During the 14-weeks Treatment period (Week 8 to Week 22)
    Title
    Percent of patients with categorized reduction from baseline in seizure frequency per week during the Treatment Period
    Description
    Categories as follows: <-25%, -25% to <25%, 25% to <50%, 50% to <75%, 75% to <100%, and 100%
    Time Frame
    From Baseline to the 14-weeks Treatment period
    Title
    Change from baseline in the average duration of seizure free intervals
    Description
    Intervals are defined as seizure-free if no seizures are reported.
    Time Frame
    From Baseline to the 14-weeks Treatment period
    Title
    Number of seizure free days during the Treatment Period
    Description
    A day is regarded as seizure-free if no seizures are reported.
    Time Frame
    During the 14-weeks Treatment period (Week 8 to Week 22)
    Title
    Absolute change from baseline in partial onset seizure frequency per week during the Treatment Period
    Description
    Absolute change from baseline in partial onset seizure frequency during the Treatment Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Time Frame
    Baseline, During the 14-weeks Treatment period (Week 8 to Week 22)
    Title
    Absolute change from baseline in partial onset seizure frequency per week during the Titration Period
    Description
    Absolute change from baseline in partial onset seizure frequency during the Titration Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Time Frame
    Baseline, During the 6-weeks Titration period (Week 8 to Week 14)
    Title
    Absolute change from baseline in partial onset seizure frequency per week during the Evaluation Period
    Description
    Absolute change from baseline in partial onset seizure frequency during the Evaluation Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Time Frame
    Baseline, During the 8-weeks Evaluation period (Week 14 to Week 22)
    Title
    Percent change from baseline in partial onset seizure frequency per week during the Treatment Period
    Description
    Percent change from baseline in partial onset seizure frequency during the Treatment Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Time Frame
    Baseline, During the 14-weeks Treatment period (Week 8 to Week 22)
    Title
    Percent change from baseline in partial onset seizure frequency per week during the Titration Period
    Description
    Percent change from baseline in partial onset seizure frequency during the Titration Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Time Frame
    Baseline, During the 6-weeks Titration period (Week 8 to Week 14)
    Title
    Percent change from baseline in partial onset seizure frequency per week during the Evaluation Period
    Description
    Percent change from baseline in partial onset seizure frequency during the Evaluation Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline.
    Time Frame
    Baseline, During the 8-weeks Evaluation period (Week 14 to Week 22)
    Title
    Cumulative percentage of patients who were seizure-free since the beginning of the Evaluation Period
    Description
    A subject was regarded as seizure-free if not seizures were reported since the beginning of the Evaluation Period.
    Time Frame
    Beginning of the Evaluation Period (Week 14)
    Title
    Partial onset seizure frequency per week during the Titration Period
    Description
    Calculated as 7-day partial onset seizure frequency.
    Time Frame
    During the 6-weeks Titration period (Week 8 to Week 14)
    Title
    Partial onset seizure frequency per week during the Evaluation Period
    Description
    Calculated as 7-day partial onset seizure frequency.
    Time Frame
    During the 6-weeks Evaluation period (Week 8 to Week 14)
    Title
    Total seizure frequency per week (Types I + II + III) during the Treatment Period
    Description
    Calculated as 7-day partial onset seizure frequency.
    Time Frame
    During the 14-weeks Treatment period (Week 8 to Week 22)
    Title
    Total seizure frequency per week (Types I + II + III) during the Titration Period
    Description
    Calculated as 7-day partial onset seizure frequency.
    Time Frame
    During the 6-weeks Titration period (Week 8 to Week 14)
    Title
    Total seizure frequency per week (Types I + II + III) during the Evaluation Period
    Description
    Calculated as 7-day partial onset seizure frequency.
    Time Frame
    During the 6-weeks Evaluation period (Week 8 to Week 14)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    4 Years
    Maximum Age & Unit of Time
    16 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: diagnosis of epilepsy with uncontrolled partial onset seizures, whether or not secondarily generalized, and the diagnosis was >= 6 months before the Selection Visit epilepsy was classifiable according to the ILAE Classification >= 4 partial onset seizures during the 4 weeks preceding the Selection Visit and were required to have >= 4 partial onset seizures during each 4-week interval of the Baseline Period to qualify for randomization unsatisfactory current AED treatment in terms of efficacy and/or safety stable AED treatment consisting of no more than two AEDs Exclusion Criteria: treatable seizure etiology epilepsy secondary to a progressive cerebral disease or any other progressively neurodegenerative disease, including Rasmussen and Landau-Kleffner diseases history of status epilepticus which required hospitalization during 3 months prior to the Selection Visit history of or the presence of pseudo seizures current diagnosis of Lennox-Gastaut syndrome
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    UCB Cares
    Organizational Affiliation
    +1 844 599 2273 (UCB)
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    16641323
    Citation
    Glauser TA, Ayala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer LJ, Lu Z; N159 Study Group. Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology. 2006 Jun 13;66(11):1654-60. doi: 10.1212/01.wnl.0000217916.00225.3a. Epub 2006 Apr 26.
    Results Reference
    background
    PubMed Identifier
    17057745
    Citation
    Jensen FE, Bourgeois BF. Randomized trial supports use of levetiracetam adjunctive therapy to treat partial seizures in children. Nat Clin Pract Neurol. 2006 Nov;2(11):596-7. doi: 10.1038/ncpneuro0325. No abstract available.
    Results Reference
    background
    PubMed Identifier
    34033237
    Citation
    Johnson ME, McClung C, Bozorg AM. Analyses of seizure responses supportive of a novel trial design to assess efficacy of antiepileptic drugs in infants and young children with epilepsy: Post hoc analyses of pediatric levetiracetam and lacosamide trials. Epilepsia Open. 2021 Jun;6(2):359-368. doi: 10.1002/epi4.12482. Epub 2021 May 3.
    Results Reference
    derived

    Learn more about this trial

    Efficacy and Tolerability of Levetiracetam Add-On Treatment in Refractory Pediatric Patients With Partial Onset Seizures

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