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

NCT03340064 | Completed Phase 3 Results

• 1 other identifier: EP0100
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 21

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.

Conditions

Partial Seizures

Keywords

Epilepsy; Partial Seizures; Levetiracetam; Monotherapy; Adjunctive Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  From Baseline (Week 0) to Visit 6 (up to Week 6)

Secondary Outcomes (12)

• 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)

• 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 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)

Study Arms (1)

Levetiracetam

EXPERIMENTAL

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.

Drug: Levetiracetam

Interventions

Levetiracetam DRUG

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

Also known as: Keppra, E-Keppra, LEV

Levetiracetam

Eligibility Criteria

• Age: 1 Month - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Japan Co. Ltd.: lead

Study Sites (21)

Ep0100 15

Fukuoka, Japan

Location

EP0100 3

Hamamatsu, Japan

Location

EP0100 6

Izumi, Japan

Location

Ep0100 20

Kobe, Japan

Location

EP0100 2

Kodaira, Japan

Location

Ep0100 21

Kofu, Japan

Location

EP0100 7

Kōshi, Japan

Location

EP0100 9

Nagakute, Japan

Location

EP0100 5

Niigata, Japan

Location

Ep0100 14

Okayama, Japan

Location

Ep0100 13

Osaka, Japan

Location

Ep0100 12

Ōbu, Japan

Location

Ep0100 11

Ōmura, Japan

Location

Ep0100 18

Saitama, Japan

Location

EP0100 4

Sapporo, Japan

Location

Ep0100 10

Sendai, Japan

Location

Ep0100 19

Sendai, Japan

Location

Ep0100 16

Shinjuku-ku, Japan

Location

Ep0100 17

Shinjuku-ku, Japan

Location

EP0100 1

Shizuoka, Japan

Location

Ep0100 22

Toyoake, Japan

Location

MeSH Terms

Conditions

Seizures; Epilepsy

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 13, 2017
• Study Start: November 30, 2017
• Primary Completion: June 1, 2021
• Study Completion: July 28, 2023
• Last Updated: July 23, 2024
• Results First Posted: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

JP (21)