Long-Term, Follow-Up Study Of the Safety And Efficacy Of Levetiracetam In Children With Partial Onset Seizures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT00152516
First received: September 7, 2005
Last updated: February 8, 2013
Last verified: April 2010
  Purpose

To allow pediatric patients with partial onset seizures an opportunity to receive (as follow-up to studies N01009(NCT00105040)/N01103(NCT00175890) or by direct enrollment) open-label levetiracetam treatment, continue studying cognition and behavior in children, and continue collection of safety/efficacy data.


Condition Intervention Phase
Epilepsy, Partial
Drug: levetiracetam (LEV)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label, Long-Term, Follow-Up Study Of the Safety And Efficacy Of Levetiracetam In Children With Partial Onset Seizures.

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Percentage Change (Reduction) of Partial (Type I) Seizure Frequency Per Week From Baseline Over Time During Treatment Period. [ Time Frame: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) ] [ Designated as safety issue: No ]
    Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.


Secondary Outcome Measures:
  • Percentage Change (Reduction) of Total (Type I, II, III) Seizure Frequency Per Week From Baseline Over Time During Treatment Period. [ Time Frame: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) ] [ Designated as safety issue: No ]
    Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

  • Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period. [ Time Frame: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) ] [ Designated as safety issue: No ]
  • Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period. [ Time Frame: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) ] [ Designated as safety issue: No ]
  • Change (Reduction) From Baseline in Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period [ Time Frame: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) ] [ Designated as safety issue: No ]
    Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

  • Change (Reduction) From Baseline in Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period [ Time Frame: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) ] [ Designated as safety issue: No ]
    Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

  • Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase [ Time Frame: Up-titration (4 weeks); Maintenance Visits 3-4 (weeks 4-14, 6-15, or 8-16); Visits 4-5 (weeks 14-24, 15-24, or 16-24); Visits 5-6 (weeks 24-36); Visits 6-7 (weeks 36-48) ] [ Designated as safety issue: No ]

    The responder rate is defined as the number of responders. A responder is a patient with a 50% or greater change (reduction) in partial seizure frequency per week.

    Note: Rates were reported as percentages.


  • Partial Seizure (Type I) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) [ Time Frame: Subjects with up to 24 weeks of exposure ] [ Designated as safety issue: No ]
    For subjects with up to 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

  • Partial Seizure (Type I) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) [ Time Frame: Subjects with greater than 24 weeks of exposure ] [ Designated as safety issue: No ]
    For subjects with greater than 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

  • Total Seizure (Type I, II, III) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) [ Time Frame: Subjects with up to 24 weeks of exposure ] [ Designated as safety issue: No ]
    For subjects with up to 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

  • Total Seizure (Type I, II, III) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) [ Time Frame: Subjects with greater than 24 weeks of exposure ] [ Designated as safety issue: No ]
    For subjects with greater than 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

  • Total Seizure (Type I, II, III) Continuously Seizure Free During the Maintenance Period [ Time Frame: greater than or equal to 24 weeks, greater than or equal to 40 weeks ] [ Designated as safety issue: No ]

    The measure description is the product limit adjusted percent of subjects seizure free starting from the beginning of the Maintenance Period.

    The up-titration period is the up to 6 week period of increasing dose prior to the Maintenance Period. The Maintenance Period is the period of stable dosing, subsquent to the up-titration period, which could last from 42 to 48 weeks.


  • Percent of Subjects With Each Seizure Type During the Evaluation Period [ Time Frame: Evaluation period (48 weeks) ] [ Designated as safety issue: No ]

    Type I Seizure is a partial onset Seizure (see International League Against Epilepsy definitions).

    Type II Seizure is a Generalized Seizure (see International League Against Epilepsy definitions).

    Type III Seizure is a Unknown Seizure Type (see International League Against Epilepsy definitions).

    A subject could experience more than one seizure type.


  • Investigator Global Evaluation Scale [ Time Frame: End of Evaluation period (week 48 or at point of early discontinuation) ] [ Designated as safety issue: No ]
    There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change).

  • Parent/Guardian Global Evaluation Scale [ Time Frame: End of Evaluation period (week 48 or at point of early discontinuation) ] [ Designated as safety issue: No ]
    There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change).

  • Subject (>=8 Years Old) Global Evaluation Scale [ Time Frame: End of Evaluation period (week 48 or at point of early discontinuation) ] [ Designated as safety issue: No ]
    There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change).

  • Leiter-R Associated Memory (AM) Memory Screen Composite Score Change From Baseline to Visit 5 (Week 24) and Visit 7 (Week 48) (4 to 16 Year Olds) [ Time Frame: Baseline to Visit 5 (Week 24) and Visit 7 (Week 48) ] [ Designated as safety issue: Yes ]
    The Leiter-R AM battery has 10 subtests. The raw scores of the subtests are converted into scaled scores. Six composite scores are constructed from the 10 subtest scaled scores. The Memory Screen is one of them. It is composed of 2 subtests the Associated Pairs and Forward Memory. The sum of the Associated Pairs and Forward Memory subtest scaled scores are converted into a Memory composite score normally distributed with a mean and standard deviation of 100 (±15). Higher scores and positive changes from baseline are better. The range of the Memory Screen composite score is 44 to 155.

  • Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Olds) [ Time Frame: Visit 5 (Week 24) ] [ Designated as safety issue: Yes ]
    This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

  • Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Olds) [ Time Frame: Visit 7 (week 48) ] [ Designated as safety issue: Yes ]
    This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

  • Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Old) [ Time Frame: Visit 5 (week 24) ] [ Designated as safety issue: Yes ]
    This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

  • Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Old) [ Time Frame: Visit 7 (week 48) ] [ Designated as safety issue: Yes ]
    This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.


Enrollment: 255
Study Start Date: October 2004
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Levetiracetam Drug: levetiracetam (LEV)
Per protocol oral tablets or oral solution at 10 to 30mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Other Name: Keppra

  Eligibility

Ages Eligible for Study:   1 Month to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pediatric patients with partial onset seizures, with 1 to 2 anti-epileptic drugs (AEDS), with participation in previous levetiracetam pediatric studies (N01009 or N01103) or direct enrollment, for whom levetiracetam treatment will be of possible benefit

Exclusion Criteria:

  • Patients on a ketogenic diet
  • Seizures too close together to accurately count
  • Pseudoseizures
  • Status epilepticus 1 month prior Visit 1
  • Current diagnosis of Lennox-Gastaut Syndrome or epilepsy secondary to a progressing cerebral disease will be excluded from the study.
  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: NCT00152516

  Show 85 Study Locations
Sponsors and Collaborators
UCB Pharma
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493
  More Information

Additional Information:
Publications:
Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT00152516     History of Changes
Other Study ID Numbers: N01148, EudraCT number:2004-000200-40
Study First Received: September 7, 2005
Results First Received: August 27, 2009
Last Updated: February 8, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Mexico: National Institute of Public Health, Health Secretariat
Brazil: National Health Surveillance Agency
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
South Africa: Medicines Control Council
India: Ministry of Health

Keywords provided by UCB Pharma:
Partial Onset Seizures
levetiracetam
Epilepsy
Keppra

Additional relevant MeSH terms:
Epilepsies, Partial
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Etiracetam
Piracetam
Anticonvulsants
Central Nervous System Agents
Neuroprotective Agents
Nootropic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014