An Open-Label Study to Determine Safety , Tolerability, and Efficacy of Oral Lacosamide in Children With Epilepsy

Epilepsy Clinical Trial

Official title:

An Open-Label Study To Determine Safety, Tolerability And Efficacy Of Long -Term Oral Lacosamide (LCM) As Adjunctive Therapy In Children With Epilepsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00938912
• Other study ID #: SP848
• Secondary ID: 2011-001559-35
• Status: Completed
• Phase: Phase 2
• Start date: December 9, 2009
• Est. completion date: May 18, 2021

Study information

• Verified date: December 2021
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy.

Description:

SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy. In addition, the study is designed to provide continued availability of LCM to subjects who have completed the SP847 (NCT00938431) study and to subjects who have discontinued from SP847 (NCT00938431) and who, in the investigator's opinion, would benefit from long-term administration of LCM.

SP848 will be open to subjects who have participated in other LCM pediatric clinical studies in epilepsy and will also be open to up to 100 subjects enrolling directly into SP848. Permissible LCM doses in SP848 are between 2-12 mg/kg/day (oral solution [syrup]) or the corresponding tablet dose up to a maximum dose of 600 mg/day.

Subjects enrolled in SP848 have the option of remaining on the oral solution formulation of LCM or switching to the commercial tablet formulation, if feasible.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 366
• Est. completion date: May 18, 2021
• Est. primary completion date: May 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

Inclusion Criteria:

• A signed informed consent form has been obtained from the parent/legal guardian and assent has been obtained from the subject, as required

• Subject and caregiver (which may be a parent, legal guardian, or other delegated caregiver) are willing and able to comply with all study requirements, including maintaining a daily seizure diary

Subjects who have participated in SP847 or other lacosamide (LCM) pediatric clinical studies in epilepsy must fulfill the following inclusion criteria:

• Subject has completed SP847 (or the subject discontinued SP847 due to a dose reduction or status epilepticus) for the treatment of uncontrolled partial-onset seizures, or subject has participated in other LCM pediatric clinical studies in epilepsy

• Subject is expected to benefit from participation, in the opinion of the investigator

Subjects who enroll directly into SP848 without previous participation in a LCM clinical study must fulfill the following inclusion criteria:

• Subject is >=4 years to <=17 years of age

• Subject has a diagnosis of epilepsy with partial-onset seizures

• Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with at least 2 Antiepileptic Drugs (AEDs) (concurrently or sequentially)

• Subject has been observed to have at least 2 countable seizures in the 4 week period prior to Screening

• Subject is on a stable dosage regimen of 1 to 3 AEDs

• Subject is an acceptable candidate for venipuncture

Exclusion Criteria:

• Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)

• Subject >= 6 years of age has a lifetime history of suicide attempt, or has suicidal ideation in the past 6 months

Subjects who have participated in SP847 or other LCM pediatric clinical studies in epilepsy are not permitted to enroll in the study if any of the following criteria are met:

• Subject meets either of the following:

1. Withdrawal criteria for the primary study (with the exception of subjects who discontinued due to a dose reduction or status epilepticus). For subjects entering from EP0060, if the subject (or legal guardian) withdraws consent solely due to route of LCM administration (iv) or if the subject requires more than 10 iv LCM infusions, the subject may be allowed to participant in SP848 after discussion with and agreement from the Medical Monitor

2. Ongoing serious Adverse Event (SAE)

Subjects who enroll directly into SP848 without previous participation in a LCM clinical study are not permitted to enroll in the study if any of the following criteria are met:

• Subject has ever received LCM

• Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study.

• Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion

• Subject has a known hypersensitivity to any component of the investigational medicinal product

• Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of the study

• Subject has a creatinine clearance less than 30mL/min

• Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450ms)

• Subject has hemodynamically significant heart disease (eg, heart failure)

• Subject has an arrhythmic heart condition requiring medical therapy

• Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias

• Subject has nonepileptic events, including psychogenic seizures, that could be confused with seizures. If both epileptic and nonepileptic events are present, epileptic events must be distinguished from nonepileptic phenomena

• Subject has a history of primary generalized epilepsy

• Subject is taking monoamine oxidase inhibitors-A (MAOI-A) or narcotic analgesics.

• Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen syndrome

• Subject has a known sodium channelopathy, such as Brugada syndrome

• Subject has >2x 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%)

Subjects who were directly enrolled in EP0060 for iv LCM replacement therapy or to initiate LCM treatment are not permitted to enroll in the study if any of the following criteria are met:

• Subjects have previously participated in a long-term, open-label LCM study

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Lacosamide
Lacosamide oral solution (syrup): Total daily dose between 2 mg/kg/day (1 mg/kg bid) to 12 mg/kg/day (6 mg/kg bid)
• Lacosamide
Lacosamide tablets: Total daily dose between 100 mg (50mg bid) - 600mg (300 mg bid). The maximum permissible dose of LCM will be 12 mg/kg/day or 600 mg/day.

Locations

Country	Name	City	State
Belgium	Sp848 201	Brussels
Belgium	Sp848 200	Edegem
Belgium	Sp848 203	Gent
Belgium	Sp848 202	Leuven
China	Sp848 950	Beijing
China	Sp848 953	Chang Chun
China	Sp848 951	Chongqing
China	Sp848 955	Hanzhou
China	Sp848 956	Nanchang
China	Sp848 952	Shanghai
China	Sp848 954	Shenzhen
France	Sp848 309	Paris
France	Sp848 304	Strasbourg Cedex
Germany	Sp848 403	Kork
Hungary	Sp848 701	Budapest
Hungary	Sp848 702	Budapest
Hungary	Sp848 703	Budapest
Hungary	Sp848 704	Budapest
Hungary	Sp848 705	Debrecen
Italy	Sp848 503	Messina
Italy	Sp848 502	Verona
Japan	Sp848 257	Fukuoka
Japan	Sp848 256	Hamamatsu
Japan	Sp848 255	Kodaira
Japan	Sp848 253	Koshi
Japan	Sp848 252	Niigata
Japan	Sp848 258	Okayama
Japan	Sp848 254	Osaka
Japan	Sp848 259	Osaka
Japan	Sp848 251	Shizuoka
Mexico	Sp848 101	Culiacan
Mexico	Sp848 104	Guadalajara
Mexico	Sp848 103	San Luis Potosi
Poland	Sp848 803	Bialystok
Poland	Sp848 807	Katowice
Poland	Sp848 804	Kielce
Poland	Sp848 801	Krakow
Poland	Sp848 805	Lublin
Ukraine	Sp848 224	Dnipropetrovs'k
Ukraine	Sp848 225	Dnipropetrovs'k
Ukraine	Sp848 220	Ivano-Frankivs'k
Ukraine	Sp848 221	Kiev
Ukraine	Sp848 222	Kiev
Ukraine	Sp848 226	Kiev
Ukraine	Sp848 223	Vinnytsia
United States	Sp848 053	Akron	Ohio
United States	Sp848 057	Augusta	Georgia
United States	Sp848 026	Austin	Texas
United States	Sp848 064	Birmingham	Alabama
United States	Sp848 068	Cincinnati	Ohio
United States	Sp848 067	Dallas	Texas
United States	Sp848 005	Durham	North Carolina
United States	Sp848 062	Hackensack	New Jersey
United States	Sp848 022	Houston	Texas
United States	Sp848 008	Kansas City	Missouri
United States	Sp848 061	Las Vegas	Nevada
United States	Sp848 059	Los Angeles	California
United States	Sp848 004	Nashville	Tennessee
United States	Sp848 015	New Brunswick	New Jersey
United States	Sp848 020	Norfolk	Virginia
United States	Sp848 054	Orlando	Florida
United States	Sp848 001	Philadelphia	Pennsylvania
United States	Sp848 016	Pittsburgh	Pennsylvania
United States	Sp848 025	Sacramento	California
United States	Sp848 006	Saint Paul	Minnesota
United States	Sp848 063	Saint Paul	Minnesota
United States	Sp848 012	Tampa	Florida
United States	Sp848 002	Washington	District of Columbia
United States	Sp848 019	Wellington	Florida

Sponsors (1)

Lead Sponsor	Collaborator
UCB BIOSCIENCES, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  China,  France,  Germany,  Hungary,  Italy,  Japan,  Mexico,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)	An AE is any untoward medical occurrence in a participant or clinical investigation study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.	From Baseline to End of Safety Follow-Up (up to 4.3 years)
Primary	Number of Participants With Serious Adverse Events (SAEs)	SAE was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in participant hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment with parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above.	From Baseline to End of Safety Follow-Up (up to 4.3 years)
Primary	Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event	TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.	From Baseline to End of Safety Follow-Up (up to 4.3 years)
Secondary	Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period	Percent change in seizure frequency per 28 days (PCH) from the Baseline value (B) to Treatment Period interval (T) was defined as:PCH = [(SFT - SFB)/SFB] x 100 where, SFT corresponded to seizure frequency during Treatment Period for relative interval in open-label study and SFB corresponded to Baseline seizure frequency. For both periods, the frequency was standardized to the number of seizures per 28 days. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count case report form/electronic case report form (CRF/eCRF) module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060.	From Baseline to End of Treatment Period (up to 4.2 years)
Secondary	Percentage of Participants With =50% Reduction in 28-day Partial-onset Seizure Frequency	A 50% responder is a participant experiencing a =50% reduction in partial-onset seizure frequency per 28 days from Baseline to end of the specified time interval, otherwise a participant is a non-responder. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count CRF/eCRF module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060.	From Baseline to End of Treatment Period (up to 4.2 years)
Secondary	Percentage of Participants With =75% Reduction in 28-day Partial-onset Seizure Frequency	A 75% responder is a participant experiencing a =75% reduction in partial-onset seizure frequency per 28 days from Baseline to end of the specified time interval, otherwise a participant is a non-responder. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count CRF/eCRF module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060.	From Baseline to End of Treatment Period (up to 4.2 years)
Secondary	Number of Seizure Days Per 28 Days for Participants With Generalized Seizures	A seizure day was defined as a day where any type of seizure was reported in the seizure diary and seizures were assessed. Days in the seizure diary which were marked as "not done" on the CRF/eCRF were not counted as seizure-free days.	Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96
Secondary	Percentage of Participants Who Achieved a Seizure-free Status	Study participants were considered seizure-free for a given period if they completed the period, reported zero seizures during the period, and had no more than 10% of days in the period for which seizure data were not available (ie, "not done" was noted on the Seizure Frequency CRF/eCRF module).	From Baseline to End of Treatment Period (up to 4.2 years)

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