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

• Sponsor: UCB BIOSCIENCES, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02710890
• Collaborator: (none)
• Enrollment: 103
• Locations: 23
• Arm: 1
• Actual Duration (Months): 24.9
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Lacosamide	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 30, 2017
• Actual Primary Completion Date: Jun 28, 2019
• Actual Study Completion Date: Jun 28, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 [From Screening Period (Day -7 to Day -1) up to the End-of-Study Period (up to Day 37)]

   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).

2. Percentage of Participants That Withdrew Due to Adverse Events During the Study [From Screening Period (Day -7 to Day -1) up to the End-of-Study Period (up to Day 37)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ep0060 003	Birmingham	Alabama	United States	35233
2	Ep0060 010	Little Rock	Arkansas	United States	72202
3	Ep0060 008	Loxahatchee Groves	Florida	United States	33470
4	Ep0060 009	Saint Paul	Minnesota	United States	55101
5	Ep0060 014	Henderson	Nevada	United States	89104
6	Ep0060 002	New Brunswick	New Jersey	United States	08903
7	Ep0060 006	Akron	Ohio	United States	44308
8	Ep0060 011	Cincinnati	Ohio	United States	45229
9	Ep0060 005	Dallas	Texas	United States	75235
10	Ep0060 007	San Antonio	Texas	United States	78258
11	Ep0060 400	Budapest		Hungary
12	Ep0060 401	Debrecen		Hungary
13	Ep0060 503	Messina		Italy
14	Ep0060 505	Roma		Italy
15	Ep0060 502	Verona		Italy
16	Ep0060 701	Kraków		Poland
17	Ep0060 224	Dnipro		Ukraine
18	Ep0060 225	Dnipro		Ukraine
19	Ep0060 220	Ivano-Frankivs'k		Ukraine
20	Ep0060 221	Kiev		Ukraine
21	Ep0060 222	Kiev		Ukraine
22	Ep0060 226	Kiev		Ukraine
23	Ep0060 223	Vinnytsia		Ukraine

Sponsors and Collaborators

• UCB BIOSCIENCES, Inc.

Investigators

• Study Director: UCB Cares, [phone] (UCB)

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 21, 2019
• Study Protocol - Apr 30, 2018

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB BIOSCIENCES, Inc.
• ClinicalTrials.gov Identifier: NCT02710890
• Other Study ID Numbers: EP0060; 2014-003294-42
• First Posted: Mar 17, 2016
• Last Update Posted: Dec 16, 2020
• Last Verified: Nov 1, 2020

• 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
• Keywords provided by UCB BIOSCIENCES, Inc.: Epilepsy; pediatric; intravenous; children; Lacosamide; VIMPAT®; seizure
• Additional relevant MeSH terms: Epilepsy; Lacosamide

Study Results

Participant Flow

Recruitment Details	The study started to enroll participants in May 2017 and concluded in June 2019.
Pre-assignment Detail	Participant Flow refers to the Safety Set iv (SS-iv).

Arm/Group Title	Lacosamide Age Cohort ≥ 1 Month - < 8 Years	Lacosamide Age Cohort ≥ 8 - < 17 Years
Arm/Group Description	This arm consisted of participants who formed Cohort 2, were greater than or equal to (≥) 1 month to less than (<) 8 years of age and received at least 1 dose of intravenous (iv) lacosamide (LCM). For the first 20 participants in Cohort 2, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 2, a Data Monitoring Committee (DMC) reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated.	This arm consisted of participants who formed Cohort 1, were ≥ 8 to < 17 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 1, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 1, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2).
Period Title: Overall Study
STARTED	48	55
COMPLETED	48	55
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Lacosamide Age Cohort ≥ 1 Month - < 8 Years	Lacosamide Age Cohort ≥ 8 - < 17 Years	Total Title
Arm/Group Description	This arm consisted of participants who formed Cohort 2, were greater than or equal to (≥) 1 month to less than (<) 8 years of age and received at least 1 dose of intravenous (iv) lacosamide (LCM). For the first 20 participants in Cohort 2, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 2, a Data Monitoring Committee (DMC) reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated.	This arm consisted of participants who formed Cohort 1, were ≥ 8 to < 17 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 1, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 1, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2).
Overall Participants	48	55	103
Age (Count of Participants)
<=18 years	48 100%	55 100%	103 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.840 (2.329)	12.662 (2.409)	8.551 (5.013)
Sex: Female, Male (Count of Participants)
Female	26 54.2%	31 56.4%	57 55.3%
Male	22 45.8%	24 43.6%	46 44.7%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	1 1.8%	1 1%
Black	2 4.2%	3 5.5%	5 4.9%
White	46 95.8%	50 90.9%	96 93.2%
Other/Mixed	0 0%	1 1.8%	1 1%

Outcome Measures

1. Primary Outcome

Title	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
Description	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).
Time Frame	From Screening Period (Day -7 to Day -1) up to the End-of-Study Period (up to Day 37)

Outcome Measure Data

Analysis Population Description

The Safety Set iv (SS-iv) included study participants in the Safety Set (SS) who received at least 1 dose of EP0060 study medication iv LCM.

Arm/Group Title	Lacosamide Age Cohort ≥ 1 Month - < 8 Years (SS-iv)	Lacosamide Age Cohort ≥ 8 - < 17 Years (SS-iv)
Arm/Group Description	This arm consisted of participants who formed Cohort 2, were ≥ 1 month to < 8 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 2, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 2, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated. Participants formed the Safety Set iv (SS-iv).	This arm consisted of participants who formed Cohort 1, were ≥ 8 to < 17 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 1, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 1, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2). Participants formed the Safety Set iv (SS-iv).
Measure Participants	48	55
Number [percentage of participants]	12.5 26%	14.5 26.4%

2. Primary Outcome

Title	Percentage of Participants That Withdrew Due to Adverse Events During the Study
Description	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.
Time Frame	From Screening Period (Day -7 to Day -1) up to the End-of-Study Period (up to Day 37)

Outcome Measure Data

Analysis Population Description

The Safety Set iv (SS-iv) included study participants in the Safety Set (SS) who received at least 1 dose of EP0060 study medication iv LCM.

Arm/Group Title	Lacosamide Age Cohort ≥ 1 Month - < 8 Years (SS-iv)	Lacosamide Age Cohort ≥ 8 - < 17 Years (SS-iv)
Arm/Group Description	This arm consisted of participants who formed Cohort 2, were ≥ 1 month to < 8 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 2, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 2, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated. Participants formed the Safety Set iv (SS-iv).	This arm consisted of participants who formed Cohort 1, were ≥ 8 to < 17 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 1, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 1, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2). Participants formed the Safety Set iv (SS-iv).
Measure Participants	48	55
Number [percentage of participants]	0 0%	0 0%

Adverse Events

Time Frame	Treatment Emergent Adverse Events were reported from Visit 2/Day 1 until End of Study Period (29 to 37 days after Visit 2/Day 1).
Adverse Event Reporting Description	1 participant could experience multiple adverse events.
Arm/Group Title	Lacosamide Age Cohort ≥ 1 Month - < 8 Years (SS-iv)		Lacosamide Age Cohort ≥ 8 - < 17 Years (SS-iv)
Arm/Group Description	This arm consisted of participants who formed Cohort 2, were ≥ 1 month to < 8 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 2, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 2, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated. Participants formed the Safety Set iv (SS-iv).		This arm consisted of participants who formed Cohort 1, were ≥ 8 to < 17 years of age and received at least 1 dose of iv LCM. For the first 20 participants in Cohort 1, iv LCM has been infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. After completion of the first 20 participants in Cohort 1, a DMC reviewed the safety and tolerability data for this Cohort and made the following recommendations: the progression of the current Cohort, including iv infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2). Participants formed the Safety Set iv (SS-iv).
All Cause Mortality
	Lacosamide Age Cohort ≥ 1 Month - < 8 Years (SS-iv)		Lacosamide Age Cohort ≥ 8 - < 17 Years (SS-iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/55 (0%)
Serious Adverse Events
	Lacosamide Age Cohort ≥ 1 Month - < 8 Years (SS-iv)		Lacosamide Age Cohort ≥ 8 - < 17 Years (SS-iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Lacosamide Age Cohort ≥ 1 Month - < 8 Years (SS-iv)		Lacosamide Age Cohort ≥ 8 - < 17 Years (SS-iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/48 (6.3%)		2/55 (3.6%)
Gastrointestinal disorders
Functional gastrointestinal disorder	1/48 (2.1%)	1	0/55 (0%)	0
General disorders
Pyrexia	1/48 (2.1%)	1	0/55 (0%)	0
Infections and infestations
Respiratory tract infection	1/48 (2.1%)	1	0/55 (0%)	0
Respiratory tract infection viral	1/48 (2.1%)	1	0/55 (0%)	0
Investigations
Blood triglycerides increased	0/48 (0%)	0	2/55 (3.6%)	2
Blood cholesterol increased	0/48 (0%)	0	1/55 (1.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.