Clinical trial NCT03340064: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Partial Seizures
Keywords: Epilepsy
Partial Seizures
Levetiracetam
Monotherapy
Adjunctive Treatment
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2017-11-13
Enrollment: 38
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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%)

Primary outcomes:
measure: Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 6
timeFrame: From Baseline (Week 0) to Visit 6 (up to Week 6)
Secondary outcomes:
measure: Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 4
timeFrame: From Baseline (Week 0) to Visit 4 (up to Week 2)
measure: Percent Change in Partial Seizure Frequency Per Week From Baseline to Visit 5
timeFrame: From Baseline (Week 0) to Visit 5 (up to Week 4)
measure: Percent Change From Baseline for Each Analysis Visit in Partial Seizure Frequency Per Week on Adjunctive Therapy
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Percent Change From Baseline for Each Analysis Visit in Partial Seizure Frequency Per Week on Monotherapy
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the First Period
timeFrame: From Baseline (Week 0) to Visit 6 (up to Week 6)
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the First Period
timeFrame: From Baseline (Week 0) to Visit 6 (up to Week 6)
measure: Percentage of Participants With TEAEs Leading to Discontinuation From Study Medication During the First Period
timeFrame: From Baseline (Week 0) to Visit 6 (up to Week 6)
measure: Percentage of Participants With TEAEs During the Combined First and Second Period
timeFrame: From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295)
measure: Percentage of Participants With Treatment-emergent SAEs During the Combined First and Second Period
timeFrame: From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295)
measure: Percentage of Participants With TEAEs Leading to Discontinuation From Study Medication During the Combined First and Second Period
timeFrame: From Baseline (Week 0) to the End of Safety Follow-up (up to Week 295)
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Ep0100 15
city: Hamamatsu
country: Japan
facility: EP0100 3
city: Izumi
country: Japan
facility: EP0100 6
city: Kobe
country: Japan
facility: Ep0100 20
city: Kodaira
country: Japan
facility: EP0100 2
city: Kofu
country: Japan
facility: Ep0100 21
city: Koshi
country: Japan
facility: EP0100 7
city: Nagakute
country: Japan
facility: EP0100 9
city: Niigata
country: Japan
facility: EP0100 5
city: OBU
country: Japan
facility: Ep0100 12
city: Okayama
country: Japan
facility: Ep0100 14
city: Omura
country: Japan
facility: Ep0100 11
city: Osaka
country: Japan
facility: Ep0100 13
city: Saitama
country: Japan
facility: Ep0100 18
city: Sapporo
country: Japan
facility: EP0100 4
city: Sendai
country: Japan
facility: Ep0100 10
city: Sendai
country: Japan
facility: Ep0100 19
city: Shinjuku-ku
country: Japan
facility: Ep0100 16
city: Shinjuku-ku
country: Japan
facility: Ep0100 17
city: Shizuoka
country: Japan
facility: EP0100 1
city: Toyoake
country: Japan
facility: Ep0100 22
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References: