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

• ClinicalTrials.gov Identifier: NCT00615615
• Recruitment Status: Completed
• First Posted: February 14, 2008
• Last Update Posted: July 30, 2020
• Sponsor: UCB Pharma
• Information provided by: UCB Pharma

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.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Levetiracetam; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 1999
• Actual Primary Completion Date: March 2003
• Actual Study Completion Date: March 2003

Arms and Interventions

Arm	Intervention/treatment
Experimental: Levetiracetam (LEV); 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.	Drug: Levetiracetam; 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
Placebo Comparator: Placebo; Subjects received Placebo matching to LEV treatment.	Drug: Placebo; Placebo tablets for oral administration that were identical in appearance to the respective formulations (LTTW and HTTW) were used as reference therapy

Outcome Measures

Primary Outcome Measures :

1. Partial onset seizure frequency (Type I, Type IC included) per week during the Treatment period [ Time Frame: During the 14-weeks Treatment period (Week 8 to Week 22) ]
   Calculated as 7-day partial onset seizure frequency.

Secondary Outcome Measures :

1. 50% responder rate in seizure frequency per week during the Treatment Period [ Time Frame: During the 14-weeks Treatment period (Week 8 to Week 22) ]
   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.
2. Percent of patients with categorized reduction from baseline in seizure frequency per week during the Treatment Period [ Time Frame: From Baseline to the 14-weeks Treatment period ]
   Categories as follows: <-25%, -25% to <25%, 25% to <50%, 50% to <75%, 75% to <100%, and 100%
3. Change from baseline in the average duration of seizure free intervals [ Time Frame: From Baseline to the 14-weeks Treatment period ]
   Intervals are defined as seizure-free if no seizures are reported.
4. Number of seizure free days during the Treatment Period [ Time Frame: During the 14-weeks Treatment period (Week 8 to Week 22) ]
   A day is regarded as seizure-free if no seizures are reported.
5. Absolute change from baseline in partial onset seizure frequency per week during the Treatment Period [ Time Frame: Baseline, During the 14-weeks Treatment period (Week 8 to Week 22) ]

   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.

6. Absolute change from baseline in partial onset seizure frequency per week during the Titration Period [ Time Frame: Baseline, During the 6-weeks Titration period (Week 8 to Week 14) ]

   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.

7. Absolute change from baseline in partial onset seizure frequency per week during the Evaluation Period [ Time Frame: Baseline, During the 8-weeks Evaluation period (Week 14 to Week 22) ]

   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.

8. Percent change from baseline in partial onset seizure frequency per week during the Treatment Period [ Time Frame: Baseline, During the 14-weeks Treatment period (Week 8 to Week 22) ]

   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.

9. Percent change from baseline in partial onset seizure frequency per week during the Titration Period [ Time Frame: Baseline, During the 6-weeks Titration period (Week 8 to Week 14) ]

   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.

10. Percent change from baseline in partial onset seizure frequency per week during the Evaluation Period [ Time Frame: Baseline, During the 8-weeks Evaluation period (Week 14 to Week 22) ]

    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.

11. Cumulative percentage of patients who were seizure-free since the beginning of the Evaluation Period [ Time Frame: Beginning of the Evaluation Period (Week 14) ]
    A subject was regarded as seizure-free if not seizures were reported since the beginning of the Evaluation Period.
12. Partial onset seizure frequency per week during the Titration Period [ Time Frame: During the 6-weeks Titration period (Week 8 to Week 14) ]
    Calculated as 7-day partial onset seizure frequency.
13. Partial onset seizure frequency per week during the Evaluation Period [ Time Frame: During the 6-weeks Evaluation period (Week 8 to Week 14) ]
    Calculated as 7-day partial onset seizure frequency.
14. Total seizure frequency per week (Types I + II + III) during the Treatment Period [ Time Frame: During the 14-weeks Treatment period (Week 8 to Week 22) ]
    Calculated as 7-day partial onset seizure frequency.
15. Total seizure frequency per week (Types I + II + III) during the Titration Period [ Time Frame: During the 6-weeks Titration period (Week 8 to Week 14) ]
    Calculated as 7-day partial onset seizure frequency.
16. Total seizure frequency per week (Types I + II + III) during the Evaluation Period [ Time Frame: During the 6-weeks Evaluation period (Week 8 to Week 14) ]
    Calculated as 7-day partial onset seizure frequency.

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Sponsors and Collaborators

UCB Pharma

Investigators

• Study Director: UCB Cares; +1 844 599 2273 (UCB)

More Information

Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: UCB
• ClinicalTrials.gov Identifier: NCT00615615
• Other Study ID Numbers: N159
• First Posted: February 14, 2008
• Last Update Posted: July 30, 2020
• Last Verified: July 2020

Keywords provided by UCB Pharma:

Levetiracetam; Keppra

Additional relevant MeSH terms:

Seizures; Nervous System Diseases; Neurologic Manifestations; Levetiracetam; Anticonvulsants; Nootropic Agents