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

• Sponsor: UCB BIOSCIENCES, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00938912
• Collaborator: (none)
• Enrollment: 366
• Locations: 69
• Arm: 1
• Actual Duration (Months): 137.3
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

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

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 366 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 9, 2009
• Actual Primary Completion Date: May 18, 2021
• Actual Study Completion Date: May 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lacosamide Subjects and their caregivers may chose to receive Lacosamide oral solution (syrup) or Lacosamide tablets. The maximum duration of LCM administration will be approximately 2 years.	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); Other Names: Vimpat® ; Drug: 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.; Other Names: Vimpat®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) [From Baseline to End of Safety Follow-Up (up to 4.3 years)]

   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.

2. Number of Participants With Serious Adverse Events (SAEs) [From Baseline to End of Safety Follow-Up (up to 4.3 years)]

   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.

3. Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event [From Baseline to End of Safety Follow-Up (up to 4.3 years)]

   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.

Secondary Outcome Measures

1. Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period [From Baseline to End of Treatment Period (up to 4.2 years)]

   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.

2. Percentage of Participants With ≥50% Reduction in 28-day Partial-onset Seizure Frequency [From Baseline to End of Treatment Period (up to 4.2 years)]

   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.

3. Percentage of Participants With ≥75% Reduction in 28-day Partial-onset Seizure Frequency [From Baseline to End of Treatment Period (up to 4.2 years)]

   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.

4. Number of Seizure Days Per 28 Days for Participants With Generalized Seizures [Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96]

   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.

5. Percentage of Participants Who Achieved a Seizure-free Status [From Baseline to End of Treatment Period (up to 4.2 years)]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sp848 064	Birmingham	Alabama	United States	35233
2	Sp848 059	Los Angeles	California	United States	90027-6062
3	Sp848 025	Sacramento	California	United States	95815
4	Sp848 002	Washington	District of Columbia	United States	20010
5	Sp848 054	Orlando	Florida	United States	32819
6	Sp848 012	Tampa	Florida	United States	33609
7	Sp848 019	Wellington	Florida	United States	33470
8	Sp848 057	Augusta	Georgia	United States	30912-4005
9	Sp848 063	Saint Paul	Minnesota	United States	55101
10	Sp848 006	Saint Paul	Minnesota	United States	55102
11	Sp848 008	Kansas City	Missouri	United States	64108
12	Sp848 061	Las Vegas	Nevada	United States	89052
13	Sp848 062	Hackensack	New Jersey	United States	07601
14	Sp848 015	New Brunswick	New Jersey	United States	08901
15	Sp848 005	Durham	North Carolina	United States	27710
16	Sp848 053	Akron	Ohio	United States	44308
17	Sp848 068	Cincinnati	Ohio	United States	45229
18	Sp848 001	Philadelphia	Pennsylvania	United States	19104
19	Sp848 016	Pittsburgh	Pennsylvania	United States	15201
20	Sp848 004	Nashville	Tennessee	United States	37212
21	Sp848 026	Austin	Texas	United States	78723
22	Sp848 067	Dallas	Texas	United States	75235
23	Sp848 022	Houston	Texas	United States	77076
24	Sp848 020	Norfolk	Virginia	United States	23510
25	Sp848 201	Brussels		Belgium
26	Sp848 200	Edegem		Belgium
27	Sp848 203	Gent		Belgium
28	Sp848 202	Leuven		Belgium
29	Sp848 950	Beijing		China
30	Sp848 953	Chang Chun		China
31	Sp848 951	Chongqing		China
32	Sp848 955	Hanzhou		China
33	Sp848 956	Nanchang		China
34	Sp848 952	Shanghai		China
35	Sp848 954	Shenzhen		China
36	Sp848 309	Paris		France
37	Sp848 304	Strasbourg Cedex		France
38	Sp848 403	Kork		Germany
39	Sp848 701	Budapest		Hungary
40	Sp848 702	Budapest		Hungary
41	Sp848 703	Budapest		Hungary
42	Sp848 704	Budapest		Hungary
43	Sp848 705	Debrecen		Hungary
44	Sp848 503	Messina		Italy
45	Sp848 502	Verona		Italy
46	Sp848 257	Fukuoka		Japan
47	Sp848 256	Hamamatsu		Japan
48	Sp848 255	Kodaira		Japan
49	Sp848 253	Koshi		Japan
50	Sp848 252	Niigata		Japan
51	Sp848 258	Okayama		Japan
52	Sp848 254	Osaka		Japan
53	Sp848 259	Osaka		Japan
54	Sp848 251	Shizuoka		Japan
55	Sp848 101	Culiacan		Mexico
56	Sp848 104	Guadalajara		Mexico
57	Sp848 103	San Luis Potosi		Mexico
58	Sp848 803	Bialystok		Poland
59	Sp848 807	Katowice		Poland
60	Sp848 804	Kielce		Poland
61	Sp848 801	Krakow		Poland
62	Sp848 805	Lublin		Poland
63	Sp848 224	Dnipropetrovs'k		Ukraine
64	Sp848 225	Dnipropetrovs'k		Ukraine
65	Sp848 220	Ivano-Frankivs'k		Ukraine
66	Sp848 221	Kiev		Ukraine
67	Sp848 222	Kiev		Ukraine
68	Sp848 226	Kiev		Ukraine
69	Sp848 223	Vinnytsia		Ukraine

Sponsors and Collaborators

• UCB BIOSCIENCES, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Oct 20, 2020
• Statistical Analysis Plan - Jan 15, 2021

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB BIOSCIENCES, Inc.
• ClinicalTrials.gov Identifier: NCT00938912
• Other Study ID Numbers: SP848; 2011-001559-35
• First Posted: Jul 14, 2009
• Last Update Posted: Jan 18, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by UCB BIOSCIENCES, Inc.: Lacosamide (VIMPAT)
• Additional relevant MeSH terms: Epilepsy; Lacosamide

Study Results

Participant Flow

Recruitment Details	The study started to enroll study participants in December 2009 and concluded in May 2021. Eligible study participants were allowed to roll over from study SP0847 (NCT00938431), SP0966 (NCT01969851) and EP0060 (NCT02710890) and eligible study participants were also allowed to directly enroll into the study.
Pre-assignment Detail	Total 366 participants were enrolled. Among 366, 365 participants received treatment. One participant was enrolled, but did not receive treatment prior to discontinuing due to ineligibility.

Arm/Group Title	Lacosamide (All Participants)
Arm/Group Description	Participants aged greater than or equal to (≥1) month received either lacosamide (LCM) 2-12 milligrams/kilograms/day (mg/kg/day) (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years.
Period Title: Overall Study
STARTED	365
COMPLETED	254
NOT COMPLETED	111

Baseline Characteristics

Arm/Group Title	Lacosamide (All Participants)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years.
Overall Participants	365
Age (Count of Participants)
<=18 years	365 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.28 (4.55)
Sex: Female, Male (Count of Participants)
Female	173 47.4%
Male	192 52.6%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaskan native	1 0.3%
Asian	111 30.4%
Black	26 7.1%
White	201 55.1%
Other/Mixed	26 7.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
Description	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.
Time Frame	From Baseline to End of Safety Follow-Up (up to 4.3 years)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) consisted of all enrolled study participants who took at least 1 dose of LCM in this study.

Arm/Group Title	Lacosamide (All Participants) (SS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the Safety Set (SS) which included all enrolled study participants who took at least 1 dose of LCM in this study.
Measure Participants	365
Count of Participants [Participants]	336 92.1%

2. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
Description	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.
Time Frame	From Baseline to End of Safety Follow-Up (up to 4.3 years)

Outcome Measure Data

Analysis Population Description

The SS consisted of all enrolled study participants who took at least 1 dose of LCM in this study.

Arm/Group Title	Lacosamide (All Participants) (SS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the SS which included all enrolled study participants who took at least 1 dose of LCM in this study.
Measure Participants	365
Count of Participants [Participants]	82 22.5%

3. Primary Outcome

Title	Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event
Description	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.
Time Frame	From Baseline to End of Safety Follow-Up (up to 4.3 years)

Outcome Measure Data

Analysis Population Description

The SS consisted of all enrolled study participants who took at least 1 dose of LCM in this study.

Arm/Group Title	Lacosamide (All Participants) (SS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the SS which included all enrolled study participants who took at least 1 dose of LCM in this study.
Measure Participants	365
Count of Participants [Participants]	27 7.4%

4. Secondary Outcome

Title	Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period
Description	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.
Time Frame	From Baseline to End of Treatment Period (up to 4.2 years)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Lacosamide (All Participants) (FAS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the Full Analysis Set (FAS) which included all study participants in the SS who had at least 1 completed post-Baseline seizure diary.
Measure Participants	308
Mean (Standard Deviation) [percent change]	-24.13 (112.08)

5. Secondary Outcome

Title	Percentage of Participants With ≥50% Reduction in 28-day Partial-onset Seizure Frequency
Description	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.
Time Frame	From Baseline to End of Treatment Period (up to 4.2 years)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Lacosamide (All Participants) (FAS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the FAS which included all study participants in the SS who had at least 1 completed post-Baseline seizure diary.
Measure Participants	308
Number [percentage of participants]	53.6 14.7%

6. Secondary Outcome

Title	Percentage of Participants With ≥75% Reduction in 28-day Partial-onset Seizure Frequency
Description	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.
Time Frame	From Baseline to End of Treatment Period (up to 4.2 years)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Lacosamide (All Participants) (FAS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the FAS which included all study participants in the SS who had at least 1 completed post-Baseline seizure diary.
Measure Participants	308
Number [percentage of participants]	40.3 11%

7. Secondary Outcome

Title	Number of Seizure Days Per 28 Days for Participants With Generalized Seizures
Description	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.
Time Frame	Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96

Outcome Measure Data

Analysis Population Description

The FAS consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment and number analyzed signifies participants who were evaluable at specified time points.

Arm/Group Title	Lacosamide (All Participants) (FAS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the FAS which included all study participants in the SS who had at least 1 completed post-Baseline seizure diary.
Measure Participants	47
Week 4	14.59 (11.94)
Week 8	14.83 (12.24)
Week 12	13.68 (12.62)
Week 20	12.57 (12.58)
Week 28	13.10 (12.63)
Week 36	11.43 (11.93)
Week 44	9.24 (11.23)
Week 52	10.48 (11.68)
Week 60	10.31 (11.84)
Week 72	11.15 (12.10)
Week 84	11.87 (12.45)
Week 96	10.73 (11.77)

8. Secondary Outcome

Title	Percentage of Participants Who Achieved a Seizure-free Status
Description	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).
Time Frame	From Baseline to End of Treatment Period (up to 4.2 years)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Lacosamide (All Participants) (FAS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the FAS which included all study participants in the SS who had at least 1 completed post-Baseline seizure diary.
Measure Participants	323
Number [percentage of participants]	7.4 2%

Adverse Events

Time Frame	From Baseline to End of Safety Follow-Up (up to 4.3 years)
Adverse Event Reporting Description	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.
Arm/Group Title	Lacosamide (All Participants) (SS)
Arm/Group Description	Participants aged ≥1 month received either LCM 2-12 mg/kg/day (oral solution) or 100-600 mg/day (tablet) at a level to optimize tolerability and seizure control (maximum dose of 12 mg/kg/day or 600 mg/day based on body weight, whichever was lower) for approximately 2 years. Participants formed the SS which included all enrolled study participants who took at least 1 dose of LCM in this study.
All Cause Mortality
	Lacosamide (All Participants) (SS)
	Affected / at Risk (%)	# Events
Total	1/365 (0.3%)
Serious Adverse Events
	Lacosamide (All Participants) (SS)
	Affected / at Risk (%)	# Events
Total	82/365 (22.5%)
Blood and lymphatic system disorders
Coagulopathy	1/365 (0.3%)	1
Cardiac disorders
Bradycardia	1/365 (0.3%)	1
Cyanosis	1/365 (0.3%)	1
Gastrointestinal disorders
Vomiting	8/365 (2.2%)	19
Constipation	3/365 (0.8%)	3
Diarrhoea	3/365 (0.8%)	3
Abdominal pain	2/365 (0.5%)	2
Haematemesis	2/365 (0.5%)	2
Gastritis	1/365 (0.3%)	1
Intussusception	1/365 (0.3%)	1
Mallory-Weiss syndrome	1/365 (0.3%)	1
Pancreatitis	1/365 (0.3%)	1
Traumatic tooth displacement	1/365 (0.3%)	1
General disorders
Pyrexia	4/365 (1.1%)	5
Adverse drug reaction	1/365 (0.3%)	1
Chest pain	1/365 (0.3%)	1
Hypothermia	1/365 (0.3%)	1
Sudden death	1/365 (0.3%)	1
Infections and infestations
Pneumonia	6/365 (1.6%)	6
Bronchitis	4/365 (1.1%)	4
Bronchopneumonia	3/365 (0.8%)	3
Gastroenteritis	3/365 (0.8%)	3
Sepsis	3/365 (0.8%)	3
Upper respiratory tract infection	3/365 (0.8%)	3
Urinary tract infection	3/365 (0.8%)	3
Otitis media	2/365 (0.5%)	2
Tonsillitis	2/365 (0.5%)	3
Acute tonsillitis	1/365 (0.3%)	1
Bronchiolitis	1/365 (0.3%)	1
Erythema infectiosum	1/365 (0.3%)	1
Pneumonia mycoplasmal	1/365 (0.3%)	1
Pneumonia viral	1/365 (0.3%)	1
Urinary tract infection fungal	1/365 (0.3%)	1
Viral infection	1/365 (0.3%)	2
Injury, poisoning and procedural complications
Endotracheal intubation complication	1/365 (0.3%)	1
Foreign body aspiration	1/365 (0.3%)	1
Head injury	1/365 (0.3%)	1
Limb traumatic amputation	1/365 (0.3%)	1
Skull fracture	1/365 (0.3%)	1
Investigations
Weight decreased	1/365 (0.3%)	1
Metabolism and nutrition disorders
Dehydration	4/365 (1.1%)	4
Decreased appetite	2/365 (0.5%)	2
Hyperammonaemia	1/365 (0.3%)	1
Malnutrition	1/365 (0.3%)	1
Musculoskeletal and connective tissue disorders
Atlantoaxial instability	1/365 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma, low grade	1/365 (0.3%)	1
Nervous system disorders
Convulsion	21/365 (5.8%)	29
Status epilepticus	11/365 (3%)	16
Epilepsy	6/365 (1.6%)	6
Complex partial seizures	5/365 (1.4%)	6
Partial seizures with secondary generalisation	4/365 (1.1%)	12
Partial seizures	3/365 (0.8%)	3
Seizure cluster	3/365 (0.8%)	5
Headache	2/365 (0.5%)	2
Altered state of consciousness	1/365 (0.3%)	1
Clonic convulsion	1/365 (0.3%)	1
Encephalitis autoimmune	1/365 (0.3%)	1
Grand mal convulsion	1/365 (0.3%)	1
Haemorrhage intracranial	1/365 (0.3%)	1
Lethargy	1/365 (0.3%)	1
Neurotoxicity	1/365 (0.3%)	1
Paraesthesia	1/365 (0.3%)	1
Psychomotor skills impaired	1/365 (0.3%)	1
Psychomotor hyperactivity	1/365 (0.3%)	1
Simple partial seizures	1/365 (0.3%)	2
Somnolence	1/365 (0.3%)	1
VIIth nerve paralysis	1/365 (0.3%)	1
Psychiatric disorders
Mental status changes	3/365 (0.8%)	5
Affective disorder	1/365 (0.3%)	2
Agitation	1/365 (0.3%)	1
Anxiety disorder	1/365 (0.3%)	2
Hallucination, visual	1/365 (0.3%)	1
Hallucination, auditory	1/365 (0.3%)	1
Nightmare	1/365 (0.3%)	1
Sleep disorder	1/365 (0.3%)	1
Substance-induced psychotic disorder	1/365 (0.3%)	1
Suicidal ideation	1/365 (0.3%)	1
Renal and urinary disorders
Haematuria	1/365 (0.3%)	1
Nephrolithiasis	1/365 (0.3%)	1
Nephrotic syndrome	1/365 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory distress	2/365 (0.5%)	2
Hypoxia	1/365 (0.3%)	1
Pneumonia aspiration	1/365 (0.3%)	1
Sleep apnoea syndrome	1/365 (0.3%)	1
Skin and subcutaneous tissue disorders
Drug eruption	1/365 (0.3%)	1
Rash	1/365 (0.3%)	1
Vascular disorders
Haematoma	1/365 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Lacosamide (All Participants) (SS)
	Affected / at Risk (%)	# Events
Total	291/365 (79.7%)
Gastrointestinal disorders
Vomiting	77/365 (21.1%)	149
Diarrhoea	40/365 (11%)	52
Constipation	25/365 (6.8%)	34
Nausea	25/365 (6.8%)	35
Abdominal pain	21/365 (5.8%)	32
Abdominal pain upper	19/365 (5.2%)	29
General disorders
Pyrexia	80/365 (21.9%)	126
Fatigue	21/365 (5.8%)	31
Infections and infestations
Nasopharyngitis	91/365 (24.9%)	253
Upper respiratory tract infection	86/365 (23.6%)	167
Pharyngitis	37/365 (10.1%)	48
Gastroenteritis	29/365 (7.9%)	35
Influenza	29/365 (7.9%)	38
Bronchitis	26/365 (7.1%)	40
Viral infection	21/365 (5.8%)	36
Sinusitis	20/365 (5.5%)	29
Urinary tract infection	20/365 (5.5%)	24
Ear infection	19/365 (5.2%)	27
Injury, poisoning and procedural complications
Contusion	25/365 (6.8%)	55
Metabolism and nutrition disorders
Decreased appetite	26/365 (7.1%)	28
Nervous system disorders
Somnolence	74/365 (20.3%)	100
Dizziness	69/365 (18.9%)	114
Headache	45/365 (12.3%)	97
Tremor	21/365 (5.8%)	23
Respiratory, thoracic and mediastinal disorders
Cough	36/365 (9.9%)	43

Limitations/Caveats

[Not Specified]

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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.