Study to Investigate Safety and Tolerability of Intravenous Lacosamide in Children. (ASPIRE)

A Multicenter, Open-Label Study to Investigate the Safety and Tolerability of Intravenous Lacosamide in Children (>= 1 Month to < 17 Years of Age) With Epilepsy

EP0060 is a multicenter, open-label study to evaluate the safety and tolerability of intravenous (iv) Lacosamide (LCM) in pediatric subjects >= 1 month to < 17 years of age with epilepsy.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Lacosamide

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2; Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Ep0060 400
  • Debrecen, Hungary
    • Ep0060 401
• Italy
  • Messina, Italy
    • Ep0060 503
  • Roma, Italy
    • Ep0060 505
  • Verona, Italy
    • Ep0060 502
• Poland
  • Kraków, Poland
    • Ep0060 701
• Ukraine
  • Dnipro, Ukraine
    • Ep0060 224
  • Dnipro, Ukraine
    • Ep0060 225
  • Ivano-Frankivs'k, Ukraine
    • Ep0060 220
  • Kiev, Ukraine
    • Ep0060 221
  • Kiev, Ukraine
    • Ep0060 222
  • Kiev, Ukraine
    • Ep0060 226
  • Vinnytsia, Ukraine
    • Ep0060 223
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Ep0060 003
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Ep0060 010
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Ep0060 008
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Ep0060 009
  • Nevada
    • Henderson, Nevada, United States, 89104
      • Ep0060 014
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Ep0060 002
  • Ohio
    • Akron, Ohio, United States, 44308
      • Ep0060 006
    • Cincinnati, Ohio, United States, 45229
      • Ep0060 011
  • Texas
    • Dallas, Texas, United States, 75235
      • Ep0060 005
    • San Antonio, Texas, United States, 78258
      • Ep0060 007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female from >=1 month to <17 years of age
• Subject has a diagnosis of epilepsy with partial-onset seizures or primary generalized tonic-clonic seizures

• Subject meets 1 of the following criteria:

  1. Open-label lacosmide (OLL) subject: Subject is currently receiving oral lacosmide (LCM) as adjunctive or monotherapy as participants in an open label long-term study (SP848, EP0034, or other pediatric study); OR,
  2. Prescription lacosamide (RxL) subject: Subject is currently receiving prescribed oral LCM from commercial supply (eg, VIMPAT) as adjunctive or monotherapy; OR,
  3. Initiating intravenous lacosamide (IIL) subject: Subject is not currently receiving LCM and will receive intravenous (iv) LCM as adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL subjects.

• Subject is an OLL or RxL subject and meets both of the following criteria:

  1. Subject has been administered LCM for the treatment of epilepsy for at least 2 weeks prior to Screening; AND
  2. Subject has been administered (OLL) or prescribed (RxL) oral LCM at a dose of 2 mg/kg/day to 12 mg/kg/day (for subjects <50 kg) or 100 mg/day to 600 mg/day (for subjects >=50 kg). Open-label study drug LCM (OLL) or prescribed oral LCM dose (RxL) must be stable for at least 3 days prior to first LCM infusion; OR,
• Subject is an ILL subject and is on a stable dosage regimen of at least 1 antiepileptic drug (AED). The daily dosage regimen of concomitant AED therapy must be kept constant for a period of at least 2 weeks prior to Screening.
• Subject is an acceptable candidate for venipuncture and iv infusion
• Subject is, in the opinion of the investigator, able to comply with all study requirements. Subject (or parent[s] or legal representative) is willing to comply with all study requirements
• Subject weighs >=4 kg

Exclusion Criteria:

• Subject has previously received intravenous (iv) lacosamide (LCM) in this study
• Subject has any medical, neurological, or psychiatric condition that, in the opinion of the investigator, could jeopardize the subject's health or compromise the subject's ability to participate in EP0060
• Subject has clinically significant hypotension or bradycardia in the opinion of the investigator
• Subject >=6 years of age has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by positive responses ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening

For open-label lacosamide (OLL) subjects, enrollment in EP0060 is not permitted if any of the following additional criteria are met:

- Subject has any ongoing Adverse Event (AE) in their long-term, open-label study that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate EP0060 or the subject meets any of the criteria for required withdrawal from the long-term open-label study

For prescription lacosamide (RxL) and initiating intravenous lacosamide (IIL) subjects, enrollment in EP0060 is not permitted if any of the following additional criteria are met:

• Subject has a medical condition that could reasonably be expected to interfere with drug absorption distribution, metabolism, or excretion
• Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of participation in EP0060
• Subject has creatinine clearance less than 30 mL/min
• Subject has a clinically relevant electrocardiogram (ECG) abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450 ms)
• Subject has hemodynamically significant heart disease (eg, heart failure)
• Subject has an arrhythmic heart condition requiring medical therapy, known cardiac sodium channelopathy, such as Brugada syndrome
• Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias
• Subject has an acute or subacutely progressive central nervous system disease.
• Subject has epilepsy secondary to a progressing cerebral disease or any other progressive or neurodegenerative disease (malignant brain tumor or Rasmussen syndrome)
• Lacosamide is intended for treatment of generalized convulsive status epilepticus
• Subject has diagnosis of Dravet's syndrome

For IIL subjects, enrollment in EP0060 is not permitted if the following additional criterion is met:

- Subject has been treated with LCM within the last 3 months prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lacosamide; Up to 2 age-based Cohorts with Cohort 1 including at least 40 subjects who are >=8 to <17 years. For Cohort 2 every attempt will be made to enroll 20 subjects >= 4 to < 8 years of age, 12 subjects >= 2 to < 4 years of age and 12 subjects >= 1 month to < 2 years of age. A Data Monitoring Committee (DMC) will review the safety and tolerability data for each Cohort to make the following recommendations: the progression of the current Cohort, including intravenous (iv) infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2).

Drug: Lacosamide; Pharmaceutical form: solution for infusion Concentration: 10 mg/ml Route of Administration: intravenous; Other Names: Vimpat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Adverse Event Reported Spontaneously by the Participant/or Caregiver (Including Parent/Legal Guardian) or Observed by the Investigator During the Study	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. 26 adverse events are reported splitting into at least 19 occurrences of individual pre-treatment emergent adverse events and 7 treatment emergent adverse events (TEAEs).	From Screening Period (Day -7 to Day -1) up to the End-of-Study Period (up to Day 37)
Percentage of Participants That Withdrew Due to Adverse Events During the Study	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment and led to the withdrawal of the participants from the study. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Screening Period (Day -7 to Day -1) up to the End-of-Study Period (up to Day 37)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES, Inc.

Publications and helpful links

General Publications

• Farkas MK, Beller C, Bozorg A, McClung C, Roebling R, Yates T, Yuen N, Makedonska I. Safety and tolerability of short-term infusions of intravenous lacosamide in pediatric patients with epilepsy: An open-label, phase 2/3 trial. Epilepsia Open. 2022 Dec 18. doi: 10.1002/epi4.12682. Online ahead of print.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2017
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): June 28, 2019

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 17, 2016

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Epilepsy; pediatric; children; intravenous; Lacosamide; seizure; VIMPAT®
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: EP0060; 2014-003294-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes