A 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

UCB Japan Co. Ltd.38 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Partial Seizures

Interventions

LevetiracetamDRUG

levetiracetam dry syrup 50% for oral administration and levetiracetam solution for infusion (100 mg/mL)

Eligibility

Sex: ALLMin age: 1 MonthMax age: 3 Years

Medical Language ↔ Plain English

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 1. 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 1. 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 1. 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 * The use of intermittent benzodiazepines, phenobarbitals, and phenytoins is allowed as long as the frequency is not greater than 1 single administration per week for at least 2 weeks prior to Visit 1 and throughout study participation. If benzodiazepines are used more than once a week, they must be considered as 1 of the AEDs 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 * Clinically significant deviations from reference range values for renal function or any of the other laboratory parameters required for this study, as determined by the Investigator * Clinically significant acute or chronic illness (as determined during the physical examination or from other information available to the Investigator) * Allergy to pyrrolidine derivatives or a history of multiple drug allergies * Subject is known to have a terminal illness * Subject has a disorder or condition that may interfere with the absorption, distribution, metabolism, or excretion of medications * Subject has a history of or presence of pseudoseizures * Subject has any medical condition that might interfere with the subject's study participation * Subject has ≥3x 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%)

Locations (21)

Ep0100 15

Fukuoka, Japan

EP0100 3

Hamamatsu, Japan

EP0100 6

Izumi, Japan

Outcomes

Primary Outcomes

Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 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.

Time frame: From Baseline (Week 0) to Visit 6 (up to Week 6)

Secondary Outcomes

Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 4

The percent difference in partial seizure frequency per week at Baseline and Study Visit 4 (Week 2) was computed as: {\[(Number of partial seizures per week at Baseline) minus (Number of partial seizures per week at Study Visit 4)\] 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.

Time frame: From Baseline (Week 0) to Visit 4 (up to Week 2)

Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 5

The percent difference in partial seizure frequency per week at Baseline and Study Visit 5 (Week 4) was computed as: {\[(Number of partial seizures per week at Baseline) minus (Number of partial seizures per week at Study Visit 5)\] 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.

Time frame: 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

Data from ClinicalTrials.gov

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Ep0100 20

Kobe, Japan

EP0100 2

Kodaira, Japan

Ep0100 21

Kofu, Japan

EP0100 7

Kōshi, Japan

EP0100 9

Nagakute, Japan

EP0100 5

Niigata, Japan

Ep0100 14

Okayama, Japan

...and 11 more locations

Percent difference in partial seizure frequency (PSF) per week at each Analysis Visit: {\[(Number of partial seizures per week at Baseline \[BL\]) - (Number of partial seizures per week at analysis visit X)\]/(Number of partial seizures per week at BL)}\*100. Positive value indicates reduction in PSF from BL. End of study (EOS)/early discontinuation visit (EDV) was based on last EDV and calculation of number of partial seizure per week were based on the period from the previous EDV visit. The mapping of seizure data to Analysis Visits was based on target dates of the visits. A seizure date after that of target date of an Analysis Visit n and up to that of target date of next Analysis Visit n+1 was mapped to the next Analysis Visit (n+1). Data for one participant assessed within study duration was mapped to Analysis Visit 35/Week 300 based on statistical plan.

Time frame: 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)

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

Percent difference in PSF per week on adjunctive therapy at BL and each analysis visit: {\[(Number of partial seizures per week at BL) - (Number of partial seizures per week at analysis visit X)\]/(Number of partial seizures per week at BL)}\*100. Percent difference in PSF per week from Baseline for each participant and analysis visit were mapped into 6 categories: \<0%, 0% to \<25%, 25% to \<50%, ≥50%, ≥75%, and 100%, then percentages of participants in these categories were derived using the number of participants at risk at each previous analysis visit as denominator. Positive value in percent difference from Baseline indicates reduction in PSF from Baseline. The mapping of seizure data to Analysis Visits was based on target dates of visits. A seizure date after that of target date of an Analysis Visit n and up to that of target date of next Analysis Visit n+1 was mapped to next Analysis Visit (n+1).

Time frame: 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 From Baseline for Each Analysis Visit in Partial Seizure Frequency Per Week on Monotherapy

The percent difference in partial seizure frequency per week on monotherapy at Baseline and each analysis visit was computed as: {\[(Number of partial seizures per week at Baseline) minus (Number of partial seizures per week at analysis visit X)\] 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 monotherapy. The maximum duration of study participation in monotherapy participants was shorter than in adjunctive therapy. Therefore, data at Week 288 and 300 is not reported for Monotherapy.

Time frame: 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 Monotherapy

Percent difference in PSF per week on monotherapy at BL and each analysis visit: {\[(Number of partial seizures per week at BL) - (Number of partial seizures per week at analysis visit X)\]/(Number of partial seizures per week at BL)}\*100. Percent difference in PFS per week from Baseline for each participant and analysis visit were mapped into 6 categories: \<0%, 0% to \<25%, 25% to \<50%, ≥50%, ≥75%, and 100%, then percentages of participants in these categories were derived using the number of participants at risk at each previous analysis visit as denominator. 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 monotherapy. Maximum duration of study participation in monotherapy participants was shorter than adjunctive therapy. Therefore, data at Week 288 and 300 is not reported for Monotherapy.

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the First Period

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation Participant administered a pharmaceutical product that does not necessarily have a causal relationship treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The treatment-emergent adverse events (TEAEs) were defined as those events that started on or after the date (and time) of first dose of study medication, or adverse events whose intensity worsened on or after the date (and time) of first dose of study medication.

Time frame: 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

A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that must meet 1 or more of the following criteria: Death; Life-threatening; Significant or persistent disability/incapacity; Congenital anomaly/birth defect (including that occurring in a fetus); Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or participant and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious; Initial inpatient hospitalization or prolongation of hospitalization. The TEAEs were defined as those events that started on or after the date (and time) of first dose of study medication, or adverse events whose intensity worsened on or after the date (and time) of first dose of study medication.

Time frame: 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

An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The TEAEs were defined as those events that started on or after the date (and time) of first dose of study medication, or adverse events whose intensity worsened on or after the date (and time) of first dose of study medication. TEAEs leading to discontinuation from study medication are reported.

Time frame: From Baseline (Week 0) to Visit 6 (up to Week 6)

Percentage of Participants With TEAEs During the Combined First and Second Period

Time frame: 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

Time frame: From Baseline (Week 0) to the End of 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

Time frame: From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295)