An Open-Label, Single-Arm, Multicenter Study of Levetiracetam as Monotherapy or Adjunctive Treatment of Partial Seizures in Pediatric Epileptic Subjects Ranging From 1 Month to Less Than 4 Years of Age
Overview
- Phase
- Phase 3
- Intervention
- Levetiracetam
- Conditions
- Partial Seizures
- Sponsor
- UCB Japan Co. Ltd.
- Enrollment
- 38
- Locations
- 21
- Primary Endpoint
- Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 6
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a study to confirm the efficacy of levetiracetam as adjunctive treatment or as monotherapy in pediatric epilepsy subjects aged 1 month to less than 4 years of age with partial seizures.
Detailed Description
The study will consist of 2 periods. The First Period (6 weeks drug treatment) is designed to confirm efficacy of levetiracetam (LEV), and the Second Period is designed to evaluate the long-term efficacy and safety of LEV.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must have a diagnosis of epilepsy with partial onset seizures whether or not secondarily generalized
- •Male or female from 1 month to \<4 years of age. Pre-term infants aged \<1 year are to be stratified into an appropriate age category using the best estimate of their corrected gestational age
- •For subjects on adjunctive therapy, subject must be on a stable antiepileptic drug (AED) regimen for the Selection and Evaluation Periods of the study. Minor adjustments to the dose of current AEDs are allowed only prior to Visit
- •Monotherapy subjects must not receive AED treatment, receive temporary AED treatment, or switch an AED prior to Visit 1
- •Subject weighs \>=3.0 kg
- •Subject may have Vagal Nerve Stimulation (VNS) which has been implanted for at least 6 months prior to Visit 1; the settings must be stable for at least 2 months prior to Visit
- •Activated VNS must be counted as 1 of the 2 AEDs
- •Subject must have experienced at least 2 observable partial seizures, with or without secondary generalization during each 7-day period during the 2 weeks prior to Visit
- •This time period (the 2 weeks prior to Visit 1) will be referred to as the Retrospective Baseline Period. This seizure information (including type, frequency, and date) must have been recorded on a daily record card (DRC) in order to be acceptable
- •If epilepsy surgery has been performed prior to study entry, subjects must have a documented failed epilepsy surgery outcome at least 4 weeks prior to Visit 1
Exclusion Criteria
- •Subject has been taking any medication (other than their concomitant AEDs) that influences the central nervous system (CNS) for which they had not been on a stable regimen for at least 1 month prior to Visit 1
- •Subject is taking any medication that may interfere with the absorption, distribution, metabolism, or excretion of the concomitant AEDs or levetiracetam (LEV) during the course of the study
- •Subject has received any investigational medication or device within 30 days prior to Visit 1
- •Subject has taken LEV prior to the study
- •Subjects using felbamate who have presented with clinically significant abnormalities and/or hepatic function during felbamate treatment, and subjects who are taking felbamate \<1year from the date of Visit 1
- •History of status epilepticus requiring hospitalization during the 30 days prior to Visit 1, except for status epilepticus occurring during the first 10 days of life
- •Subject has a treatable seizure etiology
- •Subject is on a ketogenic diet (concomitantly or within 30 days prior to Visit 1)
- •Subject has epilepsy secondary to progressing cerebral diseases
- •Subject has a current diagnosis of Rasmussen's syndrome, Landau-Kleffner disease or Lennox-Gastaut syndrome
Arms & Interventions
Levetiracetam
Subjects aged 1 month to \<6 months will be started on levetiracetam (LEV) 14 mg/kg/day at Visit 3. The dose may be increased by LEV 14 mg/kg/day for subjects aged 1 month to \<6 months at 2-week intervals to a maximum dose of 42 mg/kg/day. Subjects aged 6 months to \<4 years will be started on LEV 20 mg/kg/day at Visit 3. The dose may be increased by LEV 20 mg/kg/day at 2-week intervals to a maximum dose of 60 mg/kg/day. At Visit 6, subjects may enter the Second Period or enter the Down-Titration Period followed by a Safety Follow-Up Period. Subjects who do not enter the Second Period will be down-titrated. The dose will be decreased by LEV 14 mg/kg/day for subjects aged 1 month to \<6 months or by LEV 20 mg/kg/day for subjects aged 6 months to \<4 years at 2-week intervals to 0 mg/kg/day.
Intervention: Levetiracetam
Outcomes
Primary Outcomes
Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 6
Time Frame: From Baseline (Week 0) to Visit 6 (up to Week 6)
The percent difference in partial seizure frequency per week at Baseline and Study Visit 6 (Week 6) was computed as: {\[(Number of partial seizures per week at Baseline) minus (Number of partial seizures per week at Study Visit 6)\] divided by (Number of partial seizures per week at Baseline)} multiplied by 100. A positive value in percent difference from Baseline indicates a reduction in partial seizure frequency from Baseline. Data of this outcome measure was analyzed and reported for participants on adjunctive therapy.
Secondary Outcomes
- Percentage of Participants With a Percent Change in Partial Seizure Frequency Per Week of <0%, 0% to <25%, 25% to <50%, ≥50%, ≥75%, or 100% on Monotherapy(From Baseline (Week 0), Week 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, and Safety follow-up (up to Week 295))
- Percentage of Participants With a Percent Change in Partial Seizure Frequency Per Week of <0%, 0% to <25%, 25% to <50%, ≥50%, ≥75%, or 100% on Adjunctive Therapy(From Baseline (Week 0), Week 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, EOS/EDV Week 2, EOS/EDV Week 4, and Safety follow-up (up to Week 295))
- Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 4(From Baseline (Week 0) to Visit 4 (up to Week 2))
- Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 5(From Baseline (Week 0) to Visit 5 (up to Week 4))
- Percent Change From Baseline for Each Analysis Visit in Partial Seizure Frequency Per Week on Adjunctive Therapy(From Baseline (Week 0), Week 8, 10, 12, 15, 18, 21, 24, 27, 30, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, EOS/EDV (up to Week 295), and Safety follow-up (up to Week 295))
- Percent Change From Baseline for Each Analysis Visit in Partial Seizure Frequency Per Week on Monotherapy(From Baseline (Week 0), Week 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, and Safety follow-up (up to Week 295))
- Percentage of Participants With TEAEs Leading to Discontinuation From Study Medication During the Combined First and Second Period(From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295))
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the First Period(From Baseline (Week 0) to Visit 6 (up to Week 6))
- Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the First Period(From Baseline (Week 0) to Visit 6 (up to Week 6))
- Percentage of Participants With TEAEs Leading to Discontinuation From Study Medication During the First Period(From Baseline (Week 0) to Visit 6 (up to Week 6))
- Percentage of Participants With TEAEs During the Combined First and Second Period(From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295))
- Percentage of Participants With Treatment-emergent SAEs During the Combined First and Second Period(From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295))