Download PDF

Clinical Trial Results:
An Open-label, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy

Summary
EudraCT number	2012-001770-29
Trial protocol	SK HU DE ES CZ PT BE PL BG FR RO Outside EU/EEA
Global end of trial date	30 Mar 2023

Results information
Results version number	v2(current)
This version publication date	06 Mar 2024
First version publication date	14 Oct 2023
Other versions	v1
Version creation reason	Correction of full data set Alignment with final posting on ClinicalTrials.gov after NIH review.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

EP0012

ISRCTN number

US NCT number

NCT02408549

WHO universal trial number (UTN)

Sponsor organisation name

UCB BIOSCIENCES Inc.

Sponsor organisation address

8010 Arco Corporate Drive, Raleigh, United States, NC 27617

Public contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Scientific contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000402-PIP03-17

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

03 May 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

30 Mar 2023

Global end of trial reached?

Yes

Global end of trial date

30 Mar 2023

Was the trial ended prematurely?

Main objective of the trial

Assess the safety and tolerability of lacosamide (LCM) as an adjunctive therapy for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in subjects with idiopathic generalized epilepsy (IGE) during long-term exposure.

Protection of trial subjects

During the conduct of the study all participants were closely monitored.

Background therapy

Concomitant therapy as permitted in the protocol.

Evidence for comparator

Not applicable

Actual start date of recruitment

03 Aug 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 15

Country: Number of subjects enrolled

Brazil: 16

Country: Number of subjects enrolled

Bulgaria: 11

Country: Number of subjects enrolled

China: 3

Country: Number of subjects enrolled

Czechia: 16

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Hungary: 12

Country: Number of subjects enrolled

Israel: 7

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Japan: 37

Country: Number of subjects enrolled

Mexico: 1

Country: Number of subjects enrolled

Poland: 16

Country: Number of subjects enrolled

Portugal: 1

Country: Number of subjects enrolled

Romania: 8

Country: Number of subjects enrolled

Russian Federation: 31

Country: Number of subjects enrolled

Slovakia: 11

Country: Number of subjects enrolled

Korea, Republic of: 6

Country: Number of subjects enrolled

Spain: 13

Country: Number of subjects enrolled

Taiwan: 2

Country: Number of subjects enrolled

United States: 24

Worldwide total number of subjects

239

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

194

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study started to enroll participants in August 2015 and concluded in March 2023. Study participants from SP0982 [NCT02408523], who met EP0012 eligibility criteria were enrolled.

Screening details

The Participant Flow refers to the Safety Set. The Safety Set included all study participants who received at least 1 dose of Investigational medicinal product (IMP) during this study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

All participants (lacosamide)

Arm description

Participants included in this treatment group received at least one dose of LCM as EP0012 protocol entry criteria. The dose range for pediatric participants weighing <50 kg is from 4 mg/kg/day (oral solution) to 12 mg/kg/day (oral solution), for pediatric participants weighing ≥50 kg, the dose range is from 200 mg/day (tablets) to 600 mg/day (tablets) and for adult participants, the dose range is from 200 mg/day to 800mg/day (tablets) during the Treatment Period. The LCM dose may be increased or decreased at the investigator’s discretion after the study participant received the first dose of LCM in the study. Pediatric participants who initially started on oral solution might have transferred to tablets at Investigator’s discretion after achieving >=50 kgs. LCM was administered orally, twice daily (bid), up to approximately 5 years. Treatment was continued for at least 2 years for adult participants and up to approximately 5 years for pediatric participants.

Arm type

Experimental

Investigational medicinal product name

Lacosamide

Investigational medicinal product code

LCM

Other name

VIMPAT

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received LCM orally, bid, at pre-defined timepoints during the Treatment Period.

Investigational medicinal product name

Lacosamide

Investigational medicinal product code

LCM

Other name

VIMPAT

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Participants received LCM orally, bid, at pre-defined timepoints during the Treatment Period.

Number of subjects in period 1	All participants (lacosamide)
Started	239
Completed	157
Not completed	82
Adverse event, serious fatal	4
Adverse event, non-fatal	15
Study terminated at site	1
Withdrawal of consent due to business trip	1
Pregnancy	1
Subject moved to another place, far from site	1
Neurology research program closing at site	1
Lost to follow-up	6
Consent withdrawn	30
Site closure	1
Lack of efficacy	17
Protocol deviation	4

Baseline characteristics

Top of page

Reporting group title

All participants (lacosamide)

Reporting group description

Reporting group values	All participants (lacosamide)	Total
Number of subjects	239	239
Age Categorical
Units: Participants
≥4-<12 years	16	16
12-<18 years	28	28
18-<65 years	194	194
≥65 years	1	1
Age Continuous
Units: Years
arithmetic mean (standard deviation)	27.9 ± 12.6	-
Sex: Female, Male
Units: Participants
Female	134	134
Male	105	105

End points

Top of page

Reporting group title

All participants (lacosamide)

Reporting group description

Primary: Number of study participants with treatment-emergent adverse events (TEAEs) over the duration of the Treatment Period

Top of page

End point title

Number of study participants with treatment-emergent adverse events (TEAEs) over the duration of the Treatment Period ^[1]

End point description

AEs were considered treatment-emergent if event had onset on or after date of first study medication dose in EP0012 and within 30 days following last study medication dose or events whose intensity worsened on or after date of first study medication dose and within 30 days following date of last study medication administration. Adverse Events were reported spontaneously by the participant and/or caregiver or observed by the investigator. The Safety Set included all study participants who received at least 1 dose of IMP during this study.

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: participants	222

No statistical analyses for this end point

Primary: Number of study participants with an increase of greater than (>)25% to 50% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of greater than (>)25% to 50% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[2]

End point description

The number of participants experiencing an increase of >25% to 50% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (absence seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	93
Units: participants	1

No statistical analyses for this end point

Primary: Number of study participants with an increase of up to 25% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of up to 25% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[3]

End point description

The number of participants experiencing an increase of up to 25% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed (N) included those participants who were evaluable for the assessment (absence seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	93
Units: participants	5

No statistical analyses for this end point

Primary: Number of study participants with new appearance of absence and/or myoclonic seizures during the Treatment Period

Top of page

End point title

Number of study participants with new appearance of absence and/or myoclonic seizures during the Treatment Period ^[4]

End point description

The number of study participants with appearance of new absence and/or myoclonic seizure types experienced during the Treatment Period but who did not experience in Combined Baseline Period or in seizure classification history, before taking LCM were reported. To determine appearance of new seizure type, the Combined Baseline Period was used. Thus, the participants who directly enrolled into EP0012, the Baseline absence, and/or myoclonic seizure data from SP0982’s 4-week Prospective Baseline Period were combined with any reported Baseline absence, and myoclonic seizure information in the daily seizure diary from EP0012 (reported before first dose in EP0012) to recalculate the study participant’s Baseline variables such as days with absence, and/or myoclonic seizures per 28 days. The Safety Set included all study participants who received at least 1 dose of IMP during this study.

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: participants
Absence seizures	3
Myoclonic seizures	5

No statistical analyses for this end point

Primary: Number of study participants withdrawn due to TEAEs

Top of page

End point title

Number of study participants withdrawn due to TEAEs ^[5]

End point description

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: participants	19

No statistical analyses for this end point

Primary: Number of study participants with an increase of >25% to 50% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of >25% to 50% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[6]

End point description

The number of participants experiencing an increase of >25% to 50% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (myoclonic seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	96
Units: participants	1

No statistical analyses for this end point

Primary: Number of study participants with an increase of >50% to 75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of >50% to 75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[7]

End point description

The number of participants experiencing an increase of >50% to 75% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (myoclonic seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	96
Units: participants	1

No statistical analyses for this end point

Primary: Number of study participants with an increase of >75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of >75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[8]

End point description

The number of participants experiencing an increase of >75% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (myoclonic seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	96
Units: participants	2

No statistical analyses for this end point

Primary: Number of study participants with an increase of up to 25% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of up to 25% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[9]

End point description

The number of participants experiencing an increase of up to 25% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (myoclonic seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	96
Units: participants	4

No statistical analyses for this end point

Primary: Number of study participants with an increase of >75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of >75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[10]

End point description

The number of participants experiencing an increase of >75% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (absence seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	93
Units: participants	0

No statistical analyses for this end point

Primary: Number of study participants with an increase of >50% to 75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Top of page

End point title

Number of study participants with an increase of >50% to 75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) ^[11]

End point description

The number of participants experiencing an increase of >50% to 75% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (absence seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	93
Units: participants	0

No statistical analyses for this end point

Primary: Percentage of study participants with at least 50% worsening in days with absence seizures

Top of page

End point title

Percentage of study participants with at least 50% worsening in days with absence seizures ^[12]

End point description

Seizure worsening was defined as a participant experiencing >=50% increase in the number of days with absence seizures per 28 days from Prospective Baseline. Percentages for seizure worsening were based on those participants who have reported a history of or an occurrence of absence seizures in Prospective Baseline or the Treatment Period. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (absence seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	92
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Primary: Percentage of study participants with at least 50% worsening in days with myoclonic seizures

Top of page

End point title

Percentage of study participants with at least 50% worsening in days with myoclonic seizures ^[13]

End point description

Seizure worsening was defined as a participant experiencing >=50% increase in the number of days with myoclonic seizures per 28 days from Prospective Baseline. Percentages for seizure worsening were based on those participants who have reported a history of or an occurrence of myoclonic seizures in Prospective Baseline or the Treatment Period. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Here, Number of participants analyzed included those participants who were evaluable for the assessment (myoclonic seizures).

End point type

Primary

End point timeframe

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	All participants (lacosamide)
Number of subjects analysed	95
Units: percentage of participants
number (not applicable)	3.2

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hemoglobin)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hemoglobin)

End point description

TEMA values are defined in the Statistical Analysis Plan (SAP) as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Hematology parameter, Hemoglobin were those that were observed post-Baseline (BL) during the Treatment Period but not present at BL. For the age range, ‘2 years (y) to <17 years’, the abnormality criteria were ‘<=95' grams/deciliter (g/dL) (Low) and ‘>160' g/dL (High). For age range, ‘>=17 years’, the abnormality Criteria were ‘<=85% of lower limit of normal (LLN)’ value (Low) and ‘>=115% of upper limit of normal (ULN)’ value (High) of Hemoglobin in blood. Safety Set was analyzed. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Hematology parameter (Hemoglobin) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Low: Week (Wk) 78 (2-<17 y) (n=7)	14.3
Low: Wk 0 (>=17 y) (n=27)	3.7
Low: Wk 2 (>=17 y) (n=195)	0.5
Low: Wk 118 (>=17 y) (n=123)	0.8
Low: Wk 166 (>=17 y) (n=81)	1.2
Low: Wk 214 (>=17 y) (n=40)	2.5
Low: TV (>=17 y) (n=123)	1.6

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hematocrit)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hematocrit)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Hematocrit were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, ‘2 years to <17 years’, the abnormality criteria were ‘<=29%’ (Low) and ‘>47%’ (High) hematocrit values. For age range, ‘>=17 years’, the abnormality criteria were ‘<=85% of LLN’ (Low) and ‘>=115% of ULN’ (High) of Hematocrit values in blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Hematology parameter (Hematocrit) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
High: Wk 22 (2-<17 y) (n=29)	6.9
High: Wk 46 (2-<17 y) (n=27)	3.7
Low: Wk 46 (>=17 y) (n=170)	1.2
Low: Wk 118 (>=17 y) (n=123)	1.6
Low: Wk 166 (>=17 y) (n=81)	1.2
Low: TV (>=17 y) (n=123)	0.8

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Basophils Absolute)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Basophils Absolute)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Basophils Absolute were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, ‘>1 month’, the abnormality criteria were '>=0.4' 10^9/L of Basophils in blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. Data for visit (Week 2) wherein at least 1 TEMA value of Hematology parameter (Basophils Absolute) observed during the study was reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	228
Units: percentage of participants
number (not applicable)	0.4

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Leukocytes)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Leukocytes)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Leukocytes were those that were observed post-BL during the Treatment Period but not present at BL. For all age ranges, the abnormality criteria were ‘<=3.0' 10^9/L (Low) and ‘>= 16.0' 10^9/L (High) of Leukocytes values in blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. Data for visit (Week 62-Low) wherein at least 1 TEMA value of Hematology parameter (Leukocytes) observed during the study was reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	191
Units: percentage of participants
number (not applicable)	0.5

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Erythrocytes)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Erythrocytes)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Erythrocytes parameter were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, ‘>=2years’, the abnormality criteria were ‘<3.5' 10^12/L of Erythrocytes value in blood. Early Termination Visit (TV) was last visit in the study (up to approximately 5 years). The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. Data for visit (Early TV) wherein at least 1 TEMA value of Hematology parameter (Erythrocytes) observed during the study was reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	59
Units: percentage of participants
number (not applicable)	1.7

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Platelets)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Platelets)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Platelet count were those that were observed post-BL during the Treatment Period but not present at BL. For the age range of ‘>1 month’, the abnormality criteria were ‘<=100' 10^9/L and ‘>=600' 10^9/L of Platelets count value. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (platelets) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Lymphocytes Absolute)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Lymphocytes Absolute)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Lymphocytes Absolute were those that were observed post-Baseline (BL) during the Treatment Period but not present at Baseline. For the age range, ‘2 years - <6 years’, the abnormality criteria were ‘<0.7’ 10^9/L (Low) and ‘>6.9’ 10^9/L (High). For age range, ‘>=6 years’, the abnormality criteria were ‘<0.6’ 10^9/L (Low) and ‘>5.0’ 10^9/L (High) for Lymphocytes Absolute in the blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Hematology parameter (Lymphocytes Absolute) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	226
Units: percentage of participants
number (not applicable)
High: Wk 2 (>=6 y) (n=226)	0.4
High: Wk 78 (>=6 y) (n=63)	3.2
High: Wk 118 (>=6 y) (n=141)	0.7

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Monocytes Absolute )

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Monocytes Absolute )

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Monocytes Absolute were those that are observed post-BL during the Treatment Period but not present at BL. For the age range, ‘>1 month’, the abnormality criteria was ‘>=2.0’ 10^9/L of Monocytes in blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Monocytes Absolute) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Neutrophils Absolute)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Neutrophils Absolute)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Neutrophils Absolute were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, ‘>1 month’, the abnormality criteria was ‘<1.5’ 10^9/L of Neutrophils in blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Hematology parameter (Neutrophils Absolute) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	228
Units: percentage of participants
number (not applicable)
<1.5: Wk 2 (>1 m) (n=228)	0.9
<1.5: Wk 22 (>1 m) (n=215)	0.5
<1.5: Wk 46 (>1 m) (n=196)	0.5
<1.5: Wk 62 (>1 m) (n=191)	0.5
<1.5: Wk 94 (>1 m) (n=162)	0.6
<1.5: Wk 214 (>1 m) (n=42)	2.4

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Eosinophils Absolute)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Eosinophils Absolute)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Eosinophils Absolute were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, ‘>1 month’, the abnormality criteria were ‘>=1.0’ 10^9/L of Eosinophils in the blood. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Hematology parameter (Eosinophils Absolute) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	228
Units: percentage of participants
number (not applicable)
>=1.0: Wk 2 (>1 month) (n=228)	0.9
>=1.0: Wk 22 (>1 month) (n=215)	0.5
>=1.0: TV (>1 month) (n=134)	1.5

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Calcium)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Calcium)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Calcium were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘1 year -<17 years’, the abnormality criteria were ‘<=1.85’ millimoles per litre (mmol/L) and ‘>=2.95’ mmol/L. For age range, ‘>=17 years’, the abnormality criteria was ‘<=1.9 mmol/L’ and ‘>=2.75 mmol/L’ of serum Calcium. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Calcium) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Sodium)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Sodium)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Sodium were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘>1 month’, the abnormality criteria were ‘<127’ mmol/L (Low) and ‘>151’ mmol/L (High) of serum Sodium. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Sodium) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Potassium)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Potassium)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Potassium were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘>=1 year’, the abnormality criteria were ‘<= 3.0’ mmol/L (Low) and ‘>= 6.0’ mmol/L (High) of serum Potassium. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. Data for visit (Week 2-High) wherein at least 1 TEMA value of Serum chemistry parameter (Potassium) observed during the study was reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	230
Units: percentage of participants
number (not applicable)	0.4

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Chloride)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Chloride)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Chloride were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘>1 month’, the abnormality criteria were ‘<=90’ mmol/L (Low) and ‘>=112’ mmol/L (High) of serum Chloride. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (Chloride) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	234
Units: percentage of participants
number (not applicable)
High: Wk 2 (>1 month) (n=234)	1.3
High: Wk 22 (>1 month) (n=218)	2.3
High: Wk 46 (>1 month) (n=198)	2.5
High: Wk 62 (>1 month) (n=194)	1.5
High: Wk 78 (>1 m) (n=65)	3.1
High: Wk 94 (>1 m) (n=165)	1.2
High: Wk 118 (>1 m) (n=145)	3.4
High: Wk 214 (>1 m) (n=43)	2.3
High: TV (>1 m) (n=145)	1.4

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Bicarbonate)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Bicarbonate)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Bicarbonate were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘>1 month-<17 years’, the abnormality criteria were ‘<15’ mmol/L (Low) and ‘>38’ mmol/L (High). For age range, ‘>=17 years’, the abnormality criteria were ‘<18’ mmol/L (Low) and ‘>38’ mmol/L (High) of serum Bicarbonate. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (Bicarbonate) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	180
Units: percentage of participants
number (not applicable)
Low: Wk 2 (>=17 y) (n=180)	1.1
Low: Wk 46 (>=17 y) (n=161)	1.2
Low: Wk 62 (>=17 y) (n=158)	1.3
Low: Wk 94 (>=17 y) (n=136)	0.7

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Creatinine)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Creatinine)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Creatinine were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘1-<10 years’, the abnormality criteria were ‘>106.8’ micromole per litre (umol/L), for ‘10-<16 years’, the abnormality criteria were ‘>159.12’ umol/L and for ‘>=16 years’, the abnormality criteria was ‘>=176.8’ umol/L for serum Creatinine. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Creatinine) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Aspartate Aminotransferase)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Aspartate Aminotransferase)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Aspartate Aminotransferase (AST) were those that were observed post- BL during the Treatment Period but not present at Baseline. For all ages, the abnormality criteria were specified as ‘≥3.0 units per litre (U/L) x ULN’ (High A), ‘≥5.0 U/L x ULN’ (High B), and ‘≥10.0 U/L x ULN’ (High C) of serum AST. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (AST) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
High A: All ages (Early TV) (n=58)	1.7
High A: All ages (TV) (n=144)	0.7
High B: All ages (TV) (n=144)	0.7
High C: All ages (TV) (n=144)	0.7

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in chemistry parameters (Total Bilirubin)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in chemistry parameters (Total Bilirubin)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Total Bilirubin were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘>1 month’, the abnormality criteria was ‘≥34.208’ umol/L of serum Bilirubin. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. Data for visit (Week 22) wherein at least 1 TEMA value of serum chemistry parameter (Total Bilirubin) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	218
Units: percentage of participants
number (not applicable)	0.5

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alanine Aminotransferase)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alanine Aminotransferase)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Alanine Aminotransferase (ALT) were those that were observed post- BL during the Treatment Period but not present at Baseline. For all ages, the abnormality criteria were specified as ‘≥3.0 U/L x ULN’ (High A), ‘≥5.0 U/L x ULN’ (High B), and ‘≥10.0 U/L x ULN’ (High C) of serum ALT. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (ALT) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	234
Units: percentage of participants
number (not applicable)
High A: All ages (Wk 2) (n=234)	0.4
High A: All ages (Wk 46) (n=198)	0.5
High A: All ages (Wk 62) (n=192)	0.5
High A: All ages (Wk 118) (n=144)	0.7
High A: All ages (TV) (n=144)	0.7
High B: All ages (Wk 2) (n=234)	0.4

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alkaline Phosphatase)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alkaline Phosphatase)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Alkaline Phosphatase were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘4 years -<10 years’, the abnormality criteria was ‘>=834 U/L’, for ’10 years -<17 years’, the abnormality criteria was ‘>=1761 U/L’ and for ‘>=17 years’, the abnormality criteria was ‘>=3.0 U/L x ULN’ of serum alkaline phosphatase. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Alkaline Phosphatase) with markedly abnormal criteria specified at any visit .

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Gamma Glutamyl Transferase)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Gamma Glutamyl Transferase)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Gamma Glutamyl Transferase (GGT) were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘1 year-<13 years’, the abnormality criteria was ‘>=66’ U/L (High A), for ’13 years-<17 years’, the abnormality criteria was ‘>=126’ U/L (High B) and for ‘>=17 years’, the abnormality criteria was ‘>=3.0 U/L x ULN’ (High C) of serum GGT. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (GGT) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
High A: TV (1-<13 y) (n=6)	16.7
High C: Wk 2 (>=17 y) (n=198)	1.0
High C: Wk 22 (>=17 y) (n=189)	0.5
High C: Wk 62 (>=17 y) (n=169)	1.8
High C: Wk 78 (>=17 y) (n=58)	3.4
High C: Wk 118 (>=17 y) (n=125)	0.8
High C: Wk 166 (>=17 y) (n=89)	1.1
High C:TV (>=17 y) (n=132)	0.8

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Glucose)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Glucose)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Glucose were those that were observed post- BL during the Treatment Period but not present at BL. For the age range, ‘>1 month-<17 years’, the abnormality criteria were from ‘<2.775’ mmol/L (Low) and ‘>=9.99’ mmol/L (High). For age range, ‘>=17 years’, the abnormality criteria were ‘<2.775’ mmol/L (Low) and ‘>=11.1’ mmol/L (High) of serum Glucose. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (Glucose) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	195
Units: percentage of participants
number (not applicable)
Low: Wk 2 (>=17 y) (n=195)	0.5
Low: Wk 62 (>=17 y) (n=168)	0.6
Low: Wk 94 (>=17 y) (n=143)	0.7
Low: Wk 118 (>=17 y) (n=123)	0.8
High: Wk 2 (>=17 y) (n=195)	1.0
High: Wk 22 (>=17 y) (n=186)	1.1
High: Wk 46 (>=17 y) (n=166)	1.2
High: Wk 62 (>=17 y) (n=168)	1.8
High: Wk 78 (>=17 y) (n=58)	3.4
High: Wk 94 (>=17 y) (n=143)	0.7
High: Wk 118 (>=17 y) (n=123)	0.8
High: Early TV (>=17 y) (n=52)	1.9

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Total Protein)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Total Protein)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Total Protein were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘1 year to <17 years’, the abnormality criteria were ‘<43’ g/L and ‘>120’ g/L. For age range, ‘>=17 years’, the abnormality criteria were ‘<43’ g/L and ‘>130’ g/L of serum protein. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Total Protein) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Albumin)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Albumin)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Albumin were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘>=1 year to <17 years’, the abnormality criteria were ‘<24’ g/L and ‘>84’ g/L and for age range, ‘>=17 years’, the abnormality criteria was ‘<26’ g/L of serum albumin. The Safety Set included all study participants who received at least 1 dose of IMP during this study. No participant had TEMA value (Albumin) with markedly abnormal criteria specified at any visit.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead electrocardiogram (ECG) parameter (QT interval)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead electrocardiogram (ECG) parameter (QT interval)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA ECG results of QT interval parameter were those that were observed post- BL during the Treatment Period but not present at BL. For the age range, ‘1 month (m)-<12 years’, the abnormality criteria were ‘>=500 milliseconds (ms)’ (Abnormal (Abn) A). For age range, ‘>=12 years’, the abnormality criteria were ‘>=500 ms’ (Abn B) or ‘>=60 ms increase from BL’ (Abn C). The abnormality in QT interval was observed at Week 0 as the participant was rolled over from SP0982 study and was constantly having abnormal ECG parameters while in SP0982 and EP0012. Safety Set was analyzed. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of ECG parameter (QT interval) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	216
Units: percentage of participants
number (not applicable)
Abn C: Wk 0 (>=12 years) (n=3)	33.3
Abn C: Wk 2 (>=12 years) (n=216)	0.5
Abn C: Wk 14 (>=12 years) (n=209)	3.3
Abn C: Wk 30 (>=12 years) (n=130)	0.8
Abn B: Wk 46 (>=12 years) (n=188)	0.5
Abn C: Wk 46 (>=12 years) (n=188)	2.7
Abn C: Wk 62 (>=12 years) (n=186)	2.2
Abn C: Wk 78 (>=12 years) (n=61)	1.6
Abn C: Wk 94 (>=12 years) (n=162)	2.5
Abn C: Wk 118 (>=12 years) (n=23)	13.0
Abn C: Wk 142 (>=12 years) (n=58)	6.9
Abn C: Wk 190 (>=12 years) (n=31)	3.2
Abn C: Early TV (>=12 years) (n=52)	3.8
Abn C: TV (>=12 years) (n=43)	2.3

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Phosphate)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Phosphate)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA laboratory results of Phosphate were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘1 year-<17 years’, the abnormality criteria were from ‘<0.5814’ mmol/L (Low) and ‘>2.3902’ mmol/L (High). For age range, ‘>=17 years’, the abnormality Criteria were ‘<=0.646’ mmol/L (Low) and ‘>=1.938’ mmol/L (High) of serum phosphate. The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of serum chemistry parameter (Phosphate) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	141
Units: percentage of participants
number (not applicable)
Low: Wk 94 (>=17 y) (n=141)	0.7
Low: Wk 118 (>=17 y) (n=123)	0.8

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (QTc(F) interval)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (QTc(F) interval)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA ECG results of QTc(F) interval were those that are observed post-BL during Treatment Period but not present at BL. For age range ‘3 years -<12 years’ and ‘>=12 years- <17 years’, abnormality criteria were from ‘>440 ms’ (Abn A) and ‘>15% increase from BL value (Abn B). For age range, ‘>=17 years’, the abnormality Criteria were ‘>450 ms’ (Abn C), ‘>480 ms’ (Abn D), ‘>500 ms’ (Abn E) or ‘>=60 ms increase from BL value (Abn F). The abnormality in QTc(F) interval was observed at Week 0 as participant was rolled over from SP0982 study and was constantly having abnormal ECG parameters while in SP0982 and EP0012. Safety Set was analyzed. N=participants who were evaluable for the assessment. 'n' = participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of QTc(F) interval observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Abn C: Wk 0 (>=17 y) (n=3)	33.3
Abn D: Wk 0 (>=17 y) (n=3)	33.3
Abn F: Wk 0 (>=17 y) (n=3)	33.3
Abn C: Wk 2 (>=17 y) (n=196)	1.5
Abn F: Wk 2 (>=17 y) (n=196)	1.0
Abn A: Wk 14 (>=12 y-<17 y) (n=18)	5.6
Abn C: Wk 14 (>=17 y) (n=191)	2.1
Abn D: Wk 14 (>=17 y) (n=191)	1.0
Abn E: Wk 14 (>=17 y) (n=191)	0.5
Abn F: Wk 14 (>=17 y) (n=191)	3.7
Abn F: Wk 30 (>=17 y) (n=118)	1.7
Abn C: Wk 46 (>=17 y) (n=172)	5.2
Abn D: Wk 46 (>=17 y) (n=172)	1.7
Abn E: Wk 46 (>=17 y) (n=172)	1.2
Abn F: Wk 46 (>=17 y) (n=172)	2.3
Abn A: Wk 62 (>=12 y-<17 y) (n=16)	6.3
Abn B: Wk 62 (>=12 y-<17 y) (n=16)	6.3
Abn C: Wk 62 (>=17 y) (n=170)	2.4
Abn D: Wk 62 (>=17 y) (n=170)	0.6
Abn F: Wk 62 (>=17 y) (n=170)	1.8
Abn F: Wk 78 (>=17 y) (n=56)	1.8
Abn C: Wk 94 (>=17 y) (n=148)	2.7
Abn D: Wk 94 (>=17 y) (n=148)	2.0
Abn E: Wk 94 (>=17 y) (n=148)	2.0
Abn F: Wk 94 (>=17 y) (n=148)	3.4
Abn C: Wk 118 (>=17 y) (n=21)	9.5
Abn F: Wk 118 (>=17 y) (n=21)	4.8
Abn C: Wk 142 (>=17 y) (n=47)	2.1
Abn F: Wk 142 (>=17 y) (n=47)	2.1
Abn C: Early TV (>=17 y) (n=49)	6.1
Abn D: Early TV (>=17 y) (n=49)	2.0
Abn E: Early TV (>=17 y) (n=49)	2.0
Abn F: Early TV (>=17 y) (n=49)	4.1
Abn C: TV (>=17 y) (n=36)	2.8
Abn F: TV (>=17 y) (n=36)	5.6

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (QTc(B) interval)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (QTc(B) interval)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA ECG results of QTc(B) interval were those that are observed post-BL during Treatment Period but not present at BL. For the age range ‘3 years -<12 years’ and ‘>=12 years- <17 years’, abnormality criteria were ‘>450 ms’ (Abn A) and ‘>15% increase from BL’ value (Abn B). For age range, ‘>=17 years’, abnormality criteria were ‘>450 ms’ (Abn C), ‘>480 ms’ (Abn D), ‘>500 ms’ (Abn E) or ‘>=60 ms increase from BL’ value (Abn F). The abnormality in QTc(B) interval was observed at Week 0 as the participant was rolled over from SP0982 study and was constantly having abnormal ECG parameters while in SP0982 and EP0012. Safety Set was analyzed. N= participants who were evaluable for the assessment. 'n'=participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of QTc(B) interval observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Abn C: Wk 0 (>=17 y) (n=3)	33.3
Abn D: Wk 0 (>=17 y) (n=3)	33.3
Abn E: Wk 0 (>=17 y) (n=3)	33.3
Abn F: Wk 0 (>=17 y) (n=3)	33.3
Abn C: Wk 2 (>=17 y) (n=196)	3.6
Abn F: Wk 2 (>=17 y) (n=196)	2.0
Abn A: Wk 14 (>=12 y-<17 y) (n=18)	5.6
Abn C: Wk 14 (>=17 y) (n=191)	5.8
Abn D: Wk 14 (>=17 y) (n=191)	1.6
Abn E: Wk 14 (>=17 y) (n=191)	1.0
Abn F: Wk 14 (>=17 y) (n=191)	3.7
Abn C: Wk 30 (>=17 y) (n=118)	2.5
Abn F: Wk 30 (>=17 y) (n=118)	1.7
Abn C: Wk 46 (>=17 y) (n=172)	7.0
Abn D: Wk 46 (>=17 y) (n=172)	2.9
Abn E: Wk 46 (>=17 y) (n=172)	1.2
Abn F: Wk 46 (>=17 y) (n=172)	3.5
Abn A: Wk 62 (>=12 y-<17 y) (n=16)	6.3
Abn B: Wk 62 (>=12 y-<17 y) (n=16)	6.3
Abn C: Wk 62 (>=17 y) (n=170)	2.4
Abn D: Wk 62 (>=17 y) (n=170)	0.6
Abn E: Wk 62 (>=17 y) (n=170)	0.6
Abn F: Wk 62 (>=17 y) (n=170)	3.5
Abn C: Wk 78 (>=17 y) (n=56)	5.4
Abn F: Wk 78 (>=17 y) (n=56)	1.8
Abn C: Wk 94 (>=17 y) (n=148)	5.4
Abn D: Wk 94 (>=17 y) (n=148)	2.0
Abn E: Wk 94 (>=17 y) (n=148)	2.0
Abn F: Wk 94 (>=17 y) (n=148)	3.4
Abn A: Wk 118 (>=12 y-<17 y) (n=2)	50.0
Abn C: Wk 118 (>=17 y) (n=21)	14.3
Abn D: Wk 118 (>=17 y) (n=21)	4.8
Abn E: Wk 118 (>=17 y) (n=21)	4.8
Abn F: Wk 118 (>=17 y) (n=21)	9.5
Abn A: Wk 142 (>=12 y-<17 y) (n=11)	9.1
Abn C: Wk 142 (>=17 y) (n=47)	8.5
Abn F: Wk 142 (>=17 y) (n=47)	4.3
Abn F: Wk 166 (>=17 y) (n=3)	33.3
Abn C: Wk 190 (>=17 y) (n=26)	7.7
Abn F: Wk 190 (>=17 y) (n=26)	3.8
Abn C: Early TV (>=17 y) (n=49)	6.1
Abn D: Early TV (>=17 y) (n=49)	2.0
Abn E: Early TV (>=17 y) (n=49)	2.0
Abn F: Early TV (>=17 y) (n=49)	6.1
Abn C: TV (>=17 y) (n=36)	2.8
Abn D: TV (>=17 y) (n=36)	2.8
Abn F: TV (>=17 y) (n=36)	5.6

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (PR interval)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (PR interval)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA ECG results of PR interval were those that were observed post- BL during the Treatment Period but not present at BL. For the age range, ‘3 years -<12 years’, the abnormality criteria were ‘>180 ms’ (Abn A) and ‘>25% increase from BL value (Abn B). For the age range, ‘>=12 years - <17 years’, the abnormality criteria were ‘>200 ms’ (Abn C) and ‘>25% increase from BL value (Abn D). For age range, ‘>=17 years’, the abnormality criteria were treatment-emergent values above ‘>200 ms’ (Abn E), ‘>220 ms’ (Abn F), or ‘>250 ms’ (Abn G). Safety Set was analyzed. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of ECG parameter (PR interval) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Abn B: Wk 2 (3 y-<12 y) (n=16)	6.3
Abn D: Wk 2 (>=12 y-<17 y) (n=20)	5.0
Abn E: Wk 2 (>=17 y) (n=196)	1.5
Abn F: Wk 2 (>=17 y) (n=196)	0.5
Abn E: Wk 14 (>=17 y) (n=191)	1.0
Abn E: Wk 30 (>=17 y) (n=117)	1.7
Abn F: Wk 30 (>=17 y) (n=117)	0.9
Abn C: Wk 46 (>=12 y-<17 y) (n=16)	6.3
Abn E: Wk 46 (>=17 y) (n=172)	1.2
Abn B: Wk 62 (3 y-<12 y) (n=10)	20.0
Abn C: Wk 62 (>=12 y-<17 y) (n=16)	6.3
Abn E: Wk 62 (>=17 y) (n=170)	2.9
Abn F: Wk 62 (>=17 y) (n=170)	0.6
Abn E: Wk 78 (>=17 y) (n=56)	5.4
Abn F: Wk 78 (>=17 y) (n=56)	1.8
Abn G: Wk 78 (>=17 y) (n=56)	1.8
Abn B: Wk 94 (3 y-<12 y) (n=7)	28.6
Abn C: Wk 94 (>=12 y-<17 y) (n=14)	7.1
Abn E: Wk 94 (>=17 y) (n=148)	2.7
Abn F: Wk 94 (>=17 y) (n=148)	0.7
Abn G: Wk 94 (>=17 y) (n=148)	0.7
Abn D: Wk 118 (>=12 y-<17 y) (n=2)	50.0
Abn E: Wk 142 (>=17 y) (n=46)	8.7
Abn F: Wk 142 (>=17 y) (n=46)	2.2
Abn E: Early TV (>=17 y) (n=49)	2.0
Abn F: Early TV (>=17 y) (n=49)	2.0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (QRS interval)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (QRS interval)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA ECG results of QRS interval were those that were observed post- BL during the Treatment Period but not present at BL. For the age range, ‘3 years -<12 years’, the abnormality criteria were ‘>100 ms’ (Abn A) and ‘>25% increase from BL’ value (Abn B). For the age range, ‘>=12 years - <17 years’, the abnormality criteria were ‘>110 ms’ (Abn C) and ‘>25% increase from BL’ (Abn D). For age range, ‘>=17 years’, the abnormality criteria were treatment-emergent values above ‘>100 ms’ (Abn E), ‘>120 ms’ (Abn F), or ‘>140 ms’ (Abn G). Safety Set was analyzed. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of ECG parameter (QRS interval) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Abn E: Wk 2 (>=17 y) (n=196)	5.1
Abn D: Wk 14 (>=12 y-<17 y) (n=18)	5.6
Abn E: Wk 14 (>=17 y) (n=191)	9.9
Abn F: Wk 14 (>=17 y) (n=191)	0.5
Abn E: Wk 30 (>=17 y) (n=118)	7.6
Abn A: Wk 46 (3 y-<12 y) (n=12)	8.3
Abn D: Wk 46 (>=12 y-<17 y) (n=16)	6.3
Abn E: Wk 46 (>=17 y) (n=172)	7.6
Abn D: Wk 62 (>=12 y-<17 y) (n=16)	6.3
Abn E: Wk 62 (>=17 y) (n=170)	10.6
Abn F: Wk 62 (>=17 y) (n=170)	1.8
Abn E: Wk 78 (>=17 y) (n=56)	8.9
Abn F: Wk 78 (>=17 y) (n=56)	1.8
Abn C: Wk 94 (>=12 y-<17 y) (n=14)	7.1
Abn D: Wk 94 (>=12 y-<17 y) (n=14)	7.1
Abn E: Wk 94 (>=17 y) (n=148)	6.1
Abn F: Wk 94 (>=17 y) (n=148)	0.7
Abn E: Wk 118 (>=17 y) (n=21)	14.3
Abn E: Wk 142 (>=17 y) (n=47)	10.6
Abn E: Early TV (>=17 y) (n=49)	10.2
Abn E: TV (>=17 y) (n=36)	5.6
Abn F: TV (>=17 y) (n=36)	5.6

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (Heart rate interval)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in 12-lead ECG parameter (Heart rate interval)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA ECG results of Heart rate interval were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘3 years -<12 years’, the abnormality criteria were ‘<60 beats per minute (bpm)’ (Abn A) and ‘>130 bpm’ (Abn B). For the age range, ‘>=12 years’, the abnormality criteria were ‘<50 bpm’ (Abn C) and ‘>120 bpm’ (Abn D). The Safety Set included all study participants who received at least 1 dose of IMP during this study. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of ECG parameter (Heart rate interval) observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	216
Units: percentage of participants
number (not applicable)
Abn C: Wk 2 (>=12 y) (n=216)	1.4
Abn C: Wk 14 (>=12 y) (n=209)	2.4
Abn C: Wk 30 (>=12 y) (n=130)	1.5
Abn C: Wk 46 (>=12 y) (n=188)	0.5
Abn D: Wk 46 (>=12 y) (n=188)	0.5
Abn C: Wk 62 (>=12 y) (n=186)	3.2
Abn D: Wk 62 (>=12 y) (n=186)	0.5
Abn C: Wk 78 (>=12 y) (n=61)	3.3
Abn C: Wk 94 (>=12 y) (n=162)	1.2
Abn C: Wk 118 (>=12 y) (n=23)	4.3
Abn D: Wk 214 (>=12 y) (n=1)	100
Abn D: TV (>=12 y) (n=43)	2.3

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Pulse Rate)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Pulse Rate)

End point description

TEMA values of Pulse rate were those that were observed post- BL during Treatment Period but not present at BL. For age range, ‘3 years -<12 years’, abnormality criteria were '<60 bpm' (Low) and '>130 bpm' (High). For age range, ’12 years - <17 years’, abnormality criteria were ‘<=50 bpm’ (Low) and ‘>=120 bpm’ (High). For age range, ‘>=17 years’, abnormality criteria were ‘<=50 bpm and a decrease from BL of >=15 bpm’ (Low A), ‘>=120 bpm and an increase from BL of >=15 bpm’ (High A), ‘<60 bpm’ (Low B) and ‘>100 bpm’ (High B). Pulse rate was reported as per positions such as ‘Supine 3 minute (Sup 3 min)’, ‘Standing 1 minute’ (Std 1 min), and ‘Standing 3 minute’ (Std 3 min). Safety Set was analyzed. N= participants who were evaluable for assessment. 'n'=participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Pulse rate observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Low B: Wk 2 (>=17 y)-Sup 3 min (n=199)	4.5
High B: Wk 2 (>=17 y)- Sup 3 min (n=199)	0.5
High: Wk 2 (>=12 y-<17 y)-Std 1 min (n=20)	5.0
Low B: Wk 2 (>=17 y)-Std 1 min (n=197)	2.5
High B: Wk 2 (>=17 y)-Std 1 min (n=197)	3.0
Low B: Wk 2 (>=17 y)-Std 3 min (n=196)	1.5
High B: Wk 2 (>=17 y)-Std 3 min (n=196)	2.6
Low A: Wk 6 (>=17 y)-Sup 3 min (n=196)	0.5
Low B: Wk 6 (>=17 y)-Sup 3 min (n=196)	4.6
High B: Wk 6 (>=17 y)-Sup 3 min (n=196)	2.0
High: Wk 6 (>=12 y-<17 y)- Std 1 min (n=21)	4.8
Low B: Wk 6 (>=17 y)- Std 1 min (n=196)	1.5
High B: Wk 6 (>=17 y)- Std 1 min (n=196)	3.1
Low A: Wk 6 (>=17 y)- Std 3 min (n=196)	0.5
Low B: Wk 6 (>=17 y)- Std 3 min (n=196)	1.0
High B: Wk 6 (>=17 y)- Std 3 min (n=196)	2.6
Low B: Wk 14 (>=17 y)- Sup 3 min (n=196)	4.1
High B: Wk 14 (>=17 y)- Sup 3 min (n=196)	1.0
High: Wk 14 (>=12 y-<17 y)- Std 1 min (n=18)	5.6
Low B: Wk 14 (>=17 y)- Std 1 min (n=195)	3.1
High B: Wk 14 (>=17 y)- Std 1 min (n=195)	2.6
Low B: Wk 14 (>=17 y)- Std 3 min (n=195)	0.5
High B: Wk 14 (>=17 y)- Std 3 min (n=195)	4.1
Low B: Wk 22 (>=17 y)- Sup 3 min (n=189)	3.2
High B: Wk 22 (>=17 y)- Sup 3 min (n=189)	0.5
High A: Wk 22 (>=17 y)- Std 1 min (n=189)	0.5
Low B: Wk 22 (>=17 y)- Std 1 min (n=189)	1.6
High B: Wk 22 (>=17 y)- Std 1 min (n=189)	4.2
Low B: Wk 22 (>=17 y)- Std 3 min (n=189)	2.1
High B: Wk 22 (>=17 y)- Std 3 min (n=189)	3.7
Low B: Wk 30 (>=17 y)- Sup 3 min (n=119)	1.7
Low B: Wk 30 (>=17 y)- Std 1 min (n=119)	5.0
High B: Wk 30 (>=17 y)- Std 1 min (n=119)	3.4
Low B: Wk 30 (>=17 y)- Std 3 min (n=119)	2.5
High B: Wk 30 (>=17 y)- Std 3 min (n=119)	1.7
Low B: Wk 38 (>=17 y)- Sup 3 min (n=108)	3.7
Low B: Wk 38 (>=17 y)- Std 1 min (n=107)	2.8
High B: Wk 38 (>=17 y)- Std 1 min (n=107)	5.6
Low B: Wk 38 (>=17 y)- Std 3 min (n=107)	0.9
High B: Wk 38 (>=17 y)- Std 3 min (n=107)	2.8
Low B: Wk 46 (>=17 y)- Sup 3 min (n=174)	5.7
High B: Wk 46 (>=17 y)- Sup 3 min (n=174)	1.7
Low A: Wk 46 (>=17 y)- Std 1 min (n=174)	0.6
High A: Wk 46 (>=17 y)- Std 1 min (n=174)	1.1
Low B: Wk 46 (>=17 y)- Std 1 min (n=174)	4.0
High B: Wk 46 (>=17 y)- Std 1 min (n=174)	5.2
Low B: Wk 46 (>=17 y)- Std 3 min (n=174)	2.9
High B: Wk 46 (>=17 y)- Std 3 min (n=174)	4.6
Low B: Wk 62 (>=17 y)- Sup 3 min (n=173)	5.2
High B: Wk 62 (>=17 y)- Sup 3 min (n=173)	2.3
Low: Wk 62 (>=12 y-<17 y)- Std 1 min (n=16)	6.3
High A: Wk 62 (>=17 y)- Std 1 min (n=173)	0.6
Low B: Wk 62 (>=17 y)- Std 1 min (n=173)	4.6
High B: Wk 62 (>=17 y)- Std 1 min (n=173)	4.0
High A: Wk 62 (>=17 y)- Std 3 min (n=173)	0.6
Low B: Wk 62 (>=17 y)- Std 3 min (n=173)	2.3
High B: Wk 62 (>=17 y)- Std 3 min (n=173)	2.9
Low B: Wk 78 (>=17 y)- Sup 3 min (n=60)	6.7
High B: Wk 78 (>=17 y)- Sup 3 min (n=60)	1.7
Low B: Wk 78 (>=17 y)- Std 1 min (n=60)	6.7
High B: Wk 78 (>=17 y)- Std 1 min (n=60)	6.7
Low B: Wk 78 (>=17 y)- Std 3 min (n=60)	6.7
High B: Wk 78 (>=17 y)- Std 3 min (n=60)	5.0
Low B: Wk 94 (>=17 y)- Sup 3 min (n=148)	6.1
High B: Wk 94 (>=17 y)- Sup 3 min (n=148)	0.7
Low B: Wk 94 (>=17 y)- Std 1 min (n=148)	2.7
High B: Wk 94 (>=17 y)- Std 1 min (n=148)	4.1
Low B: Wk 94 (>=17 y)- Std 3 min (n=148)	1.4
High B: Wk 94 (>=17 y)- Std 3 min (n=148)	2.7
Low B: Wk 118 (>=17 y)- Sup 3 min (n=92)	2.2
High B: Wk 118 (>=17 y)- Sup 3 min (n=92)	2.2
Low B: Wk 118 (>=17 y)- Std 1 min (n=90)	2.2
High B: Wk 118 (>=17 y)- Std 1 min (n=90)	3.3
Low B: Wk 118 (>=17 y)- Std 3 min (n=90)	2.2
High B: Wk 118 (>=17 y)- Std 3 min (n=90)	4.4
High A: Wk 142 (>=17 y)- Sup 3 min (n=63)	1.6
Low B: Wk 142 (>=17 y)- Sup 3 min (n=63)	6.3
High B: Wk 142 (>=17 y)- Sup 3 min (n=63)	4.8
High A: Wk 142 (>=17 y)- Std 1 min (n=63)	3.2
High B: Wk 142 (>=17 y)- Std 1 min (n=63)	7.9
High A: Wk 142 (>=17 y)- Std 3 min (n=63)	1.6
Low B: Wk 142 (>=17 y)- Std 3 min (n=63)	3.2
High B: Wk 142 (>=17 y)- Std 3 min (n=63)	7.9
Low B: Wk 166 (>=17 y)- Sup 3 min (n=52)	3.8
High B: Wk 166 (>=17 y)- Sup 3 min (n=52)	1.9
Low B: Wk 166 (>=17 y)- Std 1 min (n=51)	2.0
High B: Wk 166 (>=17 y)- Std 1 min (n=51)	5.9
High B: Wk 166 (>=17 y)- Std 3 min (n=51)	5.9
Low B: Wk 190 (>=17 y)- Sup 3 min (n=34)	2.9
High B: Wk 190 (>=17 y)- Sup 3 min (n=34)	8.8
High B: Wk 190 (>=17 y)- Std 1 min (n=34)	11.8
High B: Wk 190 (>=17 y)- Std 3 min (n=34)	17.6
High B: Wk 214 (>=17 y)- Sup 3 min (n=17)	5.9
High B: Wk 214 (>=17 y)- Std 1 min (n=17)	5.9
High B: Wk 214 (>=17 y)- Std 3 min (n=17)	5.9
Low B: Early TV (>=17 y)- Sup 3 min (n=55)	3.6
High B: Early TV (>=17 y)- Sup 3 min (n=55)	1.8
High: Early TV (>=12 y-<17 y)- Std 1 min (n=3)	33.3
Low B: Early TV (>=17 y)- Std 1 min (n=55)	3.6
High B: Early TV (>=17 y)- Std 1 min (n=55)	5.5
Low A: TV (>=17 years)- Sup 3 min (n=50)	2.0
Low B: TV (>=17 years)- Sup 3 min (n=50)	4.0
High B: TV (>=17 years)- Sup 3 min (n=50)	2.0
Low B: TV (>=17 years)- Std 1 min (n=50)	2.0
High B: TV (>=17 years)- Std 1 min (n=50)	4.0
Low B: TV (>=17 years)- Std 3 min (n=50)	2.0
High B: TV (>=17 years)- Std 3 min (n=50)	2.0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Systolic Blood Pressure)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Systolic Blood Pressure)

End point description

TEMA values of Systolic Blood Pressure (BP) results were those that were observed post- BL during the Treatment Period but not present at BL. For age range, ‘3 years -<12 years’, abnormality criteria were ‘<80 millimeters of mercury (mmHg)’ (Low) and ‘>140 mmHg’ (High). For age range, ‘>=12 years - <17 years’, abnormality criteria were ‘<90 mmHg’ (Low) and ‘>160 mmHg’ (High). For age range, ‘>=17 years’, abnormality criteria were ‘<=90 mmHg and decrease from BL of >=20 mmHg’ (Low A), ‘>=180 mmHg and increase from BL of >=20’ mmHg (High A), ‘<90 mmHg’ (Low B), ‘>140 mmHg (High B), and ‘>160 mmHg’ (High C). Systolic BP were reported as per positions such as ‘Sup 3 min’, ‘Std 1 min, and ‘Std 3 min’. Safety Set was analyzed. N= participants who were evaluable for assessment. ‘n’= signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Systolic BP observed during study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
High B: Wk 2 (>=17 y)- Sup 3 min (n=199)	3.5
Low B: Wk 2 (>=17 y)- Std 1 min (n=197)	1.0
High B: Wk 2 (>=17 y)- Std 1 min (n=197)	2.5
High B: Wk 2 (>=17 y)- Std 3 min (n=196)	3.6
High B: Wk 6 (>=17 y)- Sup 3 min (n=196)	3.1
High B: Wk 6 (>=17 y)- Std 1 min (n=196)	2.0
Low B: Wk 6 (>=17 y)- Std 3 min (n=196)	0.5
High B: Wk 6 (>=17 y)- Std 3 min (n=196)	3.6
Low B: Wk 14 (>=17 y)- Sup 3 min (n=196)	0.5
High B: Wk 14 (>=17 y)- Sup 3 min (n=196)	3.1
High B: Wk 14 (>=17 y)- Std 1 min (n=195)	3.6
High B: Wk 14 (>=17 y)- Std 3 min (n=195)	3.6
High B: Wk 22 (>=17 y)- Sup 3 min (n=189)	4.2
High B: Wk 22 (>=17 y)- Std 1 min (n=189)	4.2
High B: Wk 22 (>=17 y)- Std 3 min (n=189)	3.7
Low B: Wk 30 (>=17 y)- Sup 3 min (n=119)	0.8
High B: Wk 30 (>=17 y)- Sup 3 min (n=119)	5.9
High B: Wk 30 (>=17 y)- Std 1 min (n=119)	2.5
High B: Wk 30 (>=17 y)- Std 3 min (n=119)	5.0
Low B: Wk 38 (>=17 y)- Sup 3 min (n=108)	0.9
High B: Wk 38 (>=17 y)- Sup 3 min (n=108)	2.8
Low B: Wk 38 (>=17 y)- Std 1 min (n=107)	0.9
High B: Wk 38 (>=17 y)- Std 1 min (n=107)	2.8
High B: Wk 38 (>=17 y)- Std 3 min (n=107)	3.7
Low: Wk 46 (>=12 y-<17 y)- Sup 3 min (n=16)	6.3
High B: Wk 46 (>=17 y)- Sup 3 min (n=174)	2.9
Low: Wk 46 (>=12 y-<17 y)- Std 1 min (n=16)	6.3
High B: Wk 46 (>=17 y)- Std 1 min (n=174)	2.3
Low: Wk 46 (>=12 y-<17 y)- Std 3 min (n=16)	6.3
High B: Wk 46 (>=17 y)- Std 3 min (n=174)	3.4
High C: Wk 46 (>=17 y)- Std 3 min (n=174)	0.6
Low B: Wk 62 (>=17 y)- Sup 3 min (n=173)	0.6
High B: Wk 62 (>=17 y)- Sup 3 min (n=173)	3.5
Low: Wk 62 (>=12 y-<17 y)- Std 1 min (n=16)	6.3
Low A: Wk 62 (>=17 y)- Std 1 min (n=173)	0.6
Low B: Wk 62 (>=17 y)- Std 1 min (n=173)	0.6
High B: Wk 62 (>=17 y)- Std 1 min (n=173)	2.3
Low A: Wk 62 (>=17 y)- Std 3 min (n=173)	0.6
Low B: Wk 62 (>=17 y)- Std 3 min (n=173)	1.7
High B: Wk 62 (>=17 y)- Std 3 min (n=173)	1.2
Low A: Wk 78 (>=17 y)- Sup 3 min (n=60)	1.7
High B: Wk 78 (>=17 y)- Sup 3 min (n=60)	1.7
High B: Wk 78 (>=17 y)- Std 1 min (n=60)	1.7
High B: Wk 78 (>=17 y)- Std 3 min (n=60)	1.7
High B: Wk 94 (>=17 y)- Sup 3 min (n=148)	4.1
High B: Wk 94 (>=17 y)- Std 1 min (n=148)	4.1
High B: Wk 94 (>=17 y)- Std 3 min (n=148)	4.1
High B: Wk 118 (>=17 y)- Sup 3 min (n=92)	5.4
High C: Wk 118 (>=17 y)- Sup 3 min (n=92)	1.1
High B: Wk 118 (>=17 y)- Std 1 min (n=91)	5.5
High C: Wk 118 (>=17 y)- Std 1 min (n=91)	1.1
High B: Wk 118 (>=17 y)- Std 3 min (n=91)	6.6
High C: Wk 118 (>=17 y)- Std 3 min (n=91)	1.1
High B: Wk 142 (>=17 y)- Sup 3 min (n=63)	6.3
High B: Wk 142 (>=17 y)- Std 1 min (n=63)	6.3
High B: Wk 142 (>=17 y)- Std 3 min (n=63)	6.3
High B: Wk 166 (>=17 y)- Sup 3 min (n=52)	3.8
High B: Wk 166 (>=17 y)- Std 1 min (n=51)	7.8
High B: Wk 166 (>=17 y)- Std 3 min (n=51)	7.8
High B: Wk 190 (>=17 y)- Sup 3 min (n=34)	2.9
High B: Wk 214 (>=17 y)- Std 1 min (n=17)	5.9
High C: Wk 214 (>=17 y)- Std 1 min (n=17)	5.9
High B: Wk 214 (>=17 y)- Std 3 min (n=17)	5.9
High B: Wk 262 (>=17 y)- Std 3 min (n=1)	100
High B: Early TV (>=17 y)- Sup 3 min (n=55)	1.8
High B: Early TV (>=17 y)- Std 1 min (n=55)	1.8
High B: TV (>=17 y)- Std 1 min (n=50)	4.0
High B: TV (>=17 y)- Std 3 min (n=50)	2.0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Diastolic Blood Pressure)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Diastolic Blood Pressure)

End point description

TEMA values of Diastolic BP results were those that are observed post- BL during the Treatment Period but not present at BL. For the age range, ‘3 years -<12 years’, the abnormality criteria were '<50 mmHg' (Low) and '>80 mmHg' (High), ‘>=12 years - <17 years’, the abnormality criteria were '<=50 mmHg' (Low) and '>=105 mmHg' (High), and ‘>=17 years’, the abnormality criteria were ‘<=50 mmHg and decrease from BL of >=15 mmHg’ (Low A), ‘>=105 mmHg and increase from BL of >=15’ mmHg (High A), '<50 mmHg' (Low B), '>90 mmHg' (High B), and '>100 mmHg' (High C). Diastolic BP were reported as per positions such as ‘Sup 3 min’, ‘Std 1 min, and ‘Std 3 min’. Safety Set was analyzed. Number of participants analyzed included those participants who were evaluable for the assessment. 'n' signifies participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA value of Diastolic BP observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
Low: Wk 2 (3 y-<12 y)- Sup 3 min (n=16)	6.3
Low B: Wk 2 (>=17 y)- Sup 3 min (n=199)	0.5
High B: Wk 2 (>=17 y)- Sup 3 min (n=199)	2.5
Low: Wk 2 (3 y-<12 y)- Std 1 min (n=16)	6.3
High: Wk 2 (3 y-<12 y)- Std 1 min (n=16)	6.3
High B: Wk 2 (>=17 y)- Std 1 min (n=197)	5.1
High C: Wk 2 (>=17 y)- Std 1 min (n=197)	0.5
Low: Wk 2 (3 y-<12 y)- Std 3 min (n=16)	6.3
High: Wk 2 (3 y-<12 y)- Std 3 min (n=16)	12.5
High B: Wk 2 (>=17 y)- Std 3 min (n=196)	6.1
High C: Wk 2 (>=17 y)- Std 3 min (n=196)	0.5
Low A: Wk 6 (>=17 y)- Sup 3 min (n=196)	0.5
High B: Wk 6 (>=17 y)- Sup 3 min (n=196)	4.6
High C: Wk 6 (>=17 y)- Sup 3 min (n=196)	0.5
Low A: Wk 6 (>=17 y)- Std 1 min (n=196)	0.5
High A: Wk 6 (>=17 y)- Std 1 min (n=196)	0.5
High B: Wk 6 (>=17 y)- Std 1 min (n=196)	4.1
High C: Wk 6 (>=17 y)- Std 1 min (n=196)	0.5
High: Wk 6 (3 y-<12 y)- Std 3 min (n=14)	7.1
Low A: Wk 6 (>=17 y)- Std 3 min (n=196)	0.5
Low B: Wk 6 (>=17 y)- Std 3 min (n=196)	0.5
High B: Wk 6 (>=17 y)- Std 3 min (n=196)	6.6
High C: Wk 6 (>=17 y)- Std 3 min (n=196)	0.5
High: Wk 14 (3 y-<12 y)- Sup 3 min (n=13)	7.7
High B: Wk 14 (>=17 y)- Sup 3 min (n=196)	2.0
High C: Wk 14 (>=17 y)- Sup 3 min (n=196)	0.5
High A: Wk 14 (>=17 y)- Std 1 min (n=195)	0.5
High B: Wk 14 (>=17 y)- Std 1 min (n=195)	3.1
High C: Wk 14 (>=17 y)- Std 1 min (n=195)	1.0
High: Wk 14 (3 y-<12 y)- Std 3 min (n=12)	8.3
High B: Wk 14 (>=17 y)- Std 3 min (n=195)	4.6
High C: Wk 14 (>=17 y)- Std 3 min (n=195)	0.5
High: Wk 22 (3 y-<12 y)- Sup 3 min (n=13)	15.4
Low: Wk 22 (>=12 y-<17 y)- Sup 3 min (n=16)	6.3
High B: Wk 22 (>=17 y)- Sup 3 min (n=189)	1.6
High C: Wk 22 (>=17 y)- Sup 3 min (n=189)	0.5
High: Wk 22 (3 y-<12 y)- Std 1 min (n=13)	15.4
Low A: Wk 22 (>=17 y)- Std 1 min (n=189)	1.1
Low B: Wk 22 (>=17 y)- Std 1 min (n=189)	0.5
High B: Wk 22 (>=17 y)- Std 1 min (n=189)	7.9
High C: Wk 22 (>=17 y)- Std 1 min (n=189)	0.5
High: Wk 22 (3 y-<12 y)- Std 3 min (n=13)	7.7
Low A: Wk 22 (>=17 y)- Std 3 min (n=189)	0.5
High B: Wk 22 (>=17 y)- Std 3 min (n=189)	6.3
High C: Wk 22 (>=17 y)- Std 3 min (n=189)	1.1
High B: Wk 30 (>=17 y)- Sup 3 min (n=119)	3.4
High C: Wk 30 (>=17 y)- Sup 3 min (n=119)	0.8
High: Wk 30 (3 y-<12 y)- Std 1 min (n=7)	14.3
High A: Wk 30 (>=17 y)- Std 1 min (n=119)	0.8
High B: Wk 30 (>=17 y)- Std 1 min (n=119)	5.9
High C: Wk 30 (>=17 y)- Std 1 min (n=119)	0.8
High B: Wk 30 (>=17 y)- Std 3 min (n=119)	4.2
High B: Wk 38 (>=17 y)- Sup 3 min (n=108)	2.8
High: Wk 38 (3 y-<12 y)- Std 1 min (n=5)	20.0
High B: Wk 38 (>=17 y)- Std 1 min (n=107)	5.6
High C: Wk 38 (>=17 y)- Std 1 min (n=107)	0.9
High B: Wk 38 (>=17 y)- Std 3 min (n=107)	9.3
Low A: Wk 46 (>=17 y)- Sup 3 min (n=174)	0.6
High B: Wk 46 (>=17 y)- Sup 3 min (n=174)	4.0
Low: Wk 46 (>=12 y-<17 y)- Std 1 min (n=16)	6.3
High B: Wk 46 (>=17 y)- Std 1 min (n=174)	8.0
High C: Wk 46 (>=17 y)- Std 1 min (n=174)	0.6
High B: Wk 46 (>=17 y)- Std 3 min (n=174)	9.8
High C: Wk 46 (>=17 y)- Std 3 min (n=174)	1.1
High A: Wk 62 (>=17 y)- Sup 3 min (n=173)	0.6
High B: Wk 62 (>=17 y)- Sup 3 min (n=173)	5.2
High C: Wk 62 (>=17 y)- Sup 3 min (n=173)	1.2
High: Wk 62 (3 y-<12 y)- Std 1 min (n=10)	20.0
Low: Wk 62 (>=12 y-<17 y)- Std 1 min (n=16)	6.3
High A: Wk 62 (>=17 y)- Std 1 min (n=173)	0.6
High B: Wk 62 (>=17 y)- Std 1 min (n=173)	5.8
High C: Wk 62 (>=17 y)- Std 1 min (n=173)	1.2
Low B: Wk 62 (>=17 y)- Std 3 min (n=173)	0.6
High B: Wk 62 (>=17 y)- Std 3 min (n=173)	5.8
High C: Wk 62 (>=17 y)- Std 3 min (n=173)	0.6
Low: Wk 78 (>=12 y-<17 y)- Sup 3 min (n=6)	16.7
High B: Wk 78 (>=17 y)- Sup 3 min (n=60)	1.7
High B: Wk 78 (>=17 y)- Std 1 min (n=60)	3.3
High B: Wk 78 (>=17 y)- Std 3 min (n=60)	3.3
High C: Wk 78 (>=17 y)- Std 3 min (n=60)	1.7
High B: Wk 94 (>=17 y)- Sup 3 min (n=148)	1.4
High B: Wk 94 (>=17 y)- Std 1 min (n=148)	4.1
High: Wk 94 (3 y-<12 y)- Std 3 min (n=7)	14.3
High A: Wk 94 (>=17 y)- Std 3 min (n=148)	0.7
High B: Wk 94 (>=17 y)- Std 3 min (n=148)	4.7
High C: Wk 94 (>=17 y)- Std 3 min (n=148)	0.7
Low A: Wk 118 (>=17 y)- Sup 3 min (n=92)	1.1
High A: Wk 118 (>=17 y)- Sup 3 min (n=92)	1.1
Low B: Wk 118 (>=17 y)- Sup 3 min (n=92)	1.1
High B: Wk 118 (>=17 y)- Sup 3 min (n=92)	2.2
High C: Wk 118 (>=17 y)- Sup 3 min (n=92)	1.1
Low A: Wk 118 (>=17 y)- Std 1 min (n=91)	1.1
Low B: Wk 118 (>=17 y)- Std 1 min (n=91)	1.1
High B: Wk 118 (>=17 y)- Std 1 min (n=91)	4.4
High B: Wk 118 (>=17 y)- Std 3 min (n=91)	7.7
High B: Wk 142 (>=17 y)- Sup 3 min (n=63)	6.3
High B: Wk 142 (>=17 y)- Std 1 min (n=63)	7.9
High B: Wk 142 (>=17 y)- Std 3 min (n=63)	7.9
High B: Wk 166 (>=17 y)- Sup 3 min (n=52)	3.8
High B: Wk 166 (>=17 y)- Std 1 min (n=51)	5.9
High A: Wk 166 (>=17 y)- Std 3 min (n=51)	2.0
High B: Wk 166 (>=17 y)- Std 3 min (n=51)	11.8
High C: Wk 166 (>=17 y)- Std 3 min (n=51)	2.0
High B: Wk 190 (>=17 y)- Std 3 min (n=34)	2.9
High B: Wk 214 (>=17 y)- Sup 3 min (n=17)	5.9
High A: Wk 214 (>=17 y)- Std 1 min (n=17)	5.9
High B: Wk 214 (>=17 y)- Std 1 min (n=17)	5.9
High C: Wk 214 (>=17 y)- Std 1 min (n=17)	5.9
High A: Wk 214 (>=17 y)- Std 3 min (n=17)	5.9
High B: Wk 214 (>=17 y)- Std 3 min (n=17)	5.9
High C: Wk 214 (>=17 y)- Std 3 min (n=17)	5.9
High B: Early TV (>=17 y)- Sup 3 min (n=55)	3.6
High C: Early TV (>=17 y)- Sup 3 min (n=55)	1.8
High B: Early TV (>=17 y)- Std 1 min (n=55)	9.1
High C: Early TV (>=17 y)- Std 1 min (n=55)	1.8
High A: Early TV (>=17 y)- Std 3 min (n=55)	1.8
High B: Early TV (>=17 y)- Std 3 min (n=55)	10.9
High C: Early TV (>=17 y)- Std 3 min (n=55)	3.6
High: TV (3 y-<12 y)- Sup 3 min (n=6)	16.7
High B: TV (>=17 y)- Sup 3 min (n=50)	4.0
High B: TV (>=17 y)- Std 1 min (n=50)	2.0
High B: TV (>=17 y)- Std 3 min (n=50)	4.0
High C: TV (>=17 y)- Std 3 min (n=50)	2.0

No statistical analyses for this end point

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Body Weight)

Top of page

End point title

Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in vital sign measurements (Body Weight)

End point description

TEMA values are defined in the SAP as significant deviations from the expected range of age‐appropriate values. TEMA vital signs parameter results were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range, ‘1 month - <17 years’, the abnormality criteria were ‘<3% of normal body weight’ in Kilograms (kg) or ‘>97% of normal body weight’ in kgs. Here, ‘<3% of normal’ is presented as ‘Low’ and ‘>97% of normal’ is presented as ‘High’. For the age range ‘>=17 years’, the abnormality criteria were ‘Increase/decrease of >=10%’ body weight in kgs (presented as Inc/Dec A) or ‘Increase/decrease of >=7%’ body weight in kgs (presented as Inc/Dec B). Safety Set was analyzed. N= participants who were evaluable for the assessment. ‘n’= participants who were evaluable at specified time points. Data for visits wherein at least 1 TEMA body weight value observed during the study were reported in this assessment.

End point type

Secondary

End point timeframe

During the study (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	239
Units: percentage of participants
number (not applicable)
High- Wk 14 (1 m - <17 y) (n=31)	9.7
Inc/Dec A- Wk 14 (>=17 y) (n=195)	5.6
Inc/Dec B- Wk 14 (>=17 y) (n=195)	16.4
High- Wk 30 (1 m - <17 y) (n=19)	10.5
Inc/Dec A- Wk 30 (>=17 y) (n=119)	5.9
Inc/Dec B- Wk 30 (>=17 y) (n=119)	19.3
High- Wk 46 (1 m - <17 y) (n=28)	7.1
Inc/Dec A- Wk 46 (>=17 y) (n=177)	12.4
Inc/Dec B- Wk 46 (>=17 y) (n=177)	22.6
High- Wk 62 (1 m - <17 y) (n=26)	7.7
Inc/Dec A- Wk 62 (>=17 y) (n=174)	14.9
Inc/Dec B- Wk 62 (>=17 y) (n=174)	21.8
Inc/Dec A- Wk 78 (>=17 y) (n=63)	19.0
Inc/Dec B- Wk 78 (>=17 y) (n=63)	30.2
High- Wk 94 (1 m - <17 y) (n=23)	13.0
Inc/Dec A- Wk 94 (>=17 y) (n=152)	16.4
Inc/Dec B- Wk 94 (>=17 y) (n=152)	30.9
Low- Wk 118 (1 m - <17 y) (n=19)	5.3
High- Wk 118 (1 m - <17 y) (n=19)	10.5
Inc/Dec A- Wk 118 (>=17 y) (n=97)	21.6
Inc/Dec B- Wk 118 (>=17 y) (n=97)	33.0
Low- Wk 142 (1 m - <17 y) (n=13)	7.7
High- Wk 142 (1 m - <17 y) (n=13)	7.7
Inc/Dec A- Wk 142 (>=17 y) (n=77)	19.5
Inc/Dec B- Wk 142 (>=17 y) (n=77)	32.5
High- Wk 166 (1 m - <17 y) (n=10)	10.0
Inc/Dec A- Wk 166 (>=17 y) (n=60)	25.0
Inc/Dec B- Wk 166 (>=17 y) (n=60)	45.0
Low- Wk 190 (1 m - <17 y) (n=6)	16.7
Inc/Dec A- Wk 190 (>=17 y) (n=46)	26.1
Inc/Dec B- Wk 190 (>=17 y) (n=46)	50.0
Low- Wk 214 (1 m - <17 y) (n=2)	50.0
Inc/Dec A- Wk 214 (>=17 y) (n=22)	31.8
Inc/Dec B- Wk 214 (>=17 y) (n=22)	54.5
Inc/Dec A- Wk 238 (>=17 y) (n=6)	16.7
Inc/Dec B- Wk 238 (>=17 y) (n=6)	50.0
Inc/Dec A- Wk 262 (>=17 y) (n=3)	33.3
Inc/Dec B- Wk 262 (>=17 y) (n=3)	33.3
Inc/Dec A- Early TV (>=17 y) (n=57)	26.3
Inc/Dec B- Early TV (>=17 y) (n=57)	33.3
High- TV (1 m - <17 y) (n=14)	21.4
Inc/Dec A- TV (>=17 y) (n=55)	34.5
Inc/Dec B- TV (>=17 y) (n=55)	52.7

No statistical analyses for this end point

Secondary: Percent change in Primary Generalized Tonic-clonic seizure (PGTCS) frequency per 28 days from Combined Baseline

Top of page

End point title

Percent change in Primary Generalized Tonic-clonic seizure (PGTCS) frequency per 28 days from Combined Baseline

End point description

The 28-day PGTCS frequency during the relative period was subtracted from the 28-day Combined Baseline PGTCS frequency and the result was divided by 28-day Combined Baseline PGTCS frequency and the result was then multiplied by 100 to get percent change in PGTCS frequency per 28 days from Combined Baseline Period (CB) to the appropriate analysis Period. The CB was defined as the combined 12-week Historical Baseline and 4-week Prospective Baseline periods immediately prior to randomization in the study SP0982 or prior to Visit 1 (first dose) if direct enrollers in EP0012. Full Analysis Set (FAS) was a subset of the Safety Set and included all study participants with seizure diary data for at least 1 day during this study.

End point type

Secondary

End point timeframe

From Combined Baseline until end of Treatment Period (up to approximately 5 years)

End point values	All participants (lacosamide)
Number of subjects analysed	238
Units: percent change
median (full range (min-max))	-88.58 (-100.0 to 465.4)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Adverse event reporting additional description

AEs were treatment-emergent if event had onset on or after date of first study medication dose in EP0012 and within 30 days following last study medication dose or events whose intensity worsened on or after date of first study medication dose and within 30 days following date of last study medication administration. TEAEs were assessed on SS.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

All participants (lacosamide)

Reporting group description

Serious adverse events	All participants (lacosamide)
Total subjects affected by serious adverse events
subjects affected / exposed	54 / 239 (22.59%)
number of deaths (all causes)	4
number of deaths resulting from adverse events	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Uterine leiomyoma
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Vascular disorders
Peripheral ischaemia
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Drowning
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Non-cardiac chest pain
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Respiratory failure
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Psychiatric disorders
Completed suicide
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Mental status changes
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Psychogenic seizure
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Suicide attempt
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Investigations
Drug level increased
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Weight decreased
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Injury, poisoning and procedural complications
Subdural haematoma
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Head injury
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 4
deaths causally related to treatment / all	0 / 0
Facial bones fracture
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Animal bite
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ankle fracture
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Clavicle fracture
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Epidural haemorrhage
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Face injury
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Fall
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Fibula fracture
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Fracture
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hand fracture
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Intentional overdose
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Lip injury
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Periorbital contusion
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Spinal column injury
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Stab wound
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Toxicity to various agents
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Traumatic intracranial haemorrhage
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cardiac failure acute
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Nervous system disorders
Grand mal convulsion
subjects affected / exposed	16 / 239 (6.69%)
occurrences causally related to treatment / all	1 / 20
deaths causally related to treatment / all	0 / 0
Status epilepticus
subjects affected / exposed	4 / 239 (1.67%)
occurrences causally related to treatment / all	1 / 7
deaths causally related to treatment / all	0 / 0
Myoclonic epilepsy
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Petit mal epilepsy
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Benign intracranial hypertension
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Brain injury
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Convulsion
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cubital tunnel syndrome
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Dizziness
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Migraine
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Multiple sclerosis relapse
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ear and labyrinth disorders
Vertigo positional
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Periorbital oedema
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	2 / 239 (0.84%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Abdominal pain
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Abdominal pain lower
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Coeliac disease
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Small intestinal perforation
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Musculoskeletal and connective tissue disorders
Mixed connective tissue disease
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Infections and infestations
Escherichia urinary tract infection
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Infected dermal cyst
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Otitis media acute
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 239 (0.42%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	All participants (lacosamide)
Total subjects affected by non serious adverse events
subjects affected / exposed	176 / 239 (73.64%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	24 / 239 (10.04%)
occurrences all number	30
Laceration
subjects affected / exposed	12 / 239 (5.02%)
occurrences all number	14
Nervous system disorders
Grand mal convulsion
subjects affected / exposed	14 / 239 (5.86%)
occurrences all number	16
Somnolence
subjects affected / exposed	40 / 239 (16.74%)
occurrences all number	51
Dizziness
subjects affected / exposed	53 / 239 (22.18%)
occurrences all number	73
Headache
subjects affected / exposed	56 / 239 (23.43%)
occurrences all number	113
Migraine
subjects affected / exposed	13 / 239 (5.44%)
occurrences all number	17
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	13 / 239 (5.44%)
occurrences all number	13
Fatigue
subjects affected / exposed	13 / 239 (5.44%)
occurrences all number	15
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	19 / 239 (7.95%)
occurrences all number	30
Eye disorders
Diplopia
subjects affected / exposed	12 / 239 (5.02%)
occurrences all number	15
Gastrointestinal disorders
Nausea
subjects affected / exposed	23 / 239 (9.62%)
occurrences all number	31
Diarrhoea
subjects affected / exposed	18 / 239 (7.53%)
occurrences all number	23
Vomiting
subjects affected / exposed	16 / 239 (6.69%)
occurrences all number	24
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	17 / 239 (7.11%)
occurrences all number	19
Infections and infestations
Corona virus infection
subjects affected / exposed	14 / 239 (5.86%)
occurrences all number	16
Upper respiratory tract infection
subjects affected / exposed	17 / 239 (7.11%)
occurrences all number	18
Influenza
subjects affected / exposed	18 / 239 (7.53%)
occurrences all number	23
Nasopharyngitis
subjects affected / exposed	52 / 239 (21.76%)
occurrences all number	91

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Jan 2015

Global Protocol Amendment 1, dated 27 Jan 2015, provided the following primary and key revisions. No study participants entered the study prior to the date of amendment. The primary purpose of this substantial amendment followed the amendment made to the SP0982 protocol, which was to identify significant changes to the study design and the inclusion of pediatric study participants (≥4 to 12 years of age). The duration of EP0012 was clarified as at least 2 years, and LCM plasma concentration analysis was removed. Clarification on study participants being able to participate in a substudy at some sites, without being withdrawn from EP0012, was added. The use of concomitant medications and treatments was clarified and permitted and prohibited concomitant treatments were clarified to be consistent with SP0982. For pediatric study participants <50 kg, a Dispensation Visit was added 12 weeks after each 24-weekly visit from Year 3 onwards, in order to dispense LCM solution. Behavior Rating Inventory of Executive Function® - Preschool Version (BRIEF®-P) was added and socio-professional data assessment was removed in this study.

09 Jun 2016

Global Protocol Amendment 2, dated 09 Jun 2016, provided the following primary and key revisions. Thirty study participants entered the study prior to the date of amendment. The protocol was amended following a request from the Taiwanese Ministry of Health and Welfare: for dose escalation, study participants who were eligible Baseline failures from SP0982 had to remain on the dose for ≥7 days before a subsequent dose escalation. Additionally, the purpose of the amendment was to remove superfluous description of a substudy, to clarify the requirement for ECG at subsequent visits, requirement for endocrinology and timing of endocrinology assessments, pregnancy testing, definition of contraceptive methods, and seizure count, and to add a definition of the Enrolled Set (ES). Several assessments were removed from Years 3 to 5, including brief physical examination (complete physical examination instead), complete neurological examination (brief neurological examination instead), and health outcome measures. The protocol was also updated according to the new UCB protocol template, for example, with the addition of text regarding potential drug-induced liver injury (PDILI).

29 Nov 2017

Global Protocol Amendment 3, dated 29 Nov 2017, provided the following primary and key revisions. One hundred forty-four study participants entered the study prior to the date of amendment. The primary purpose of this amendment was to simplify the assessments and procedures for all study participants during the first 94 weeks of study and to simplify the assessments and procedures for adults after Week 94. Pediatric assessments were kept as they were after Week 94 for regulatory purposes. In addition, the following changes were made: • To allow the Safety Follow-up for study participants tapered in SP0982 after the 125th event occurred in SP0982; the 4-week Safety Follow-up was to be started at Visit 1 of EP0012. • In the schedule of study assessments for treatment Years 1 to 2, a footnote was added to explain that Visit 6, Visit 7, and Visit 10 were not performed according to Protocol Amendment 3. Footnote ‘b’ had ‘vital signs’ removed and for footnote ‘d,’ Week 30, Week 38, and Week 78 were added to the footnote for consistency. • A schedule of study assessments for Years 3 through 5 for EP0012 (Treatment Period, Early Termination (ET) Visit, Termination Visit, and Unscheduled Visit for study participants ≥18 years) was added. • In the schedule of study assessments for Years 3 through 5, footnotes were amended to specify that the Taper Period and Safety Follow-up Visit included some of the study participants who tapered into SP0982 after the 125th event and who consented to enter EP0012 for the Safety Follow-up Visit only. • To restructure the safety variables. • To align the planned number of study participants with the pivotal study SP0982. • To update the introduction section with regulatory information on the marketing authorization of Vimpat and to provide an update on the LCM clinical program. • To clarify the PDILI criteria requiring immediate and permanent discontinuation of the study medication.

13 Dec 2019

Global Protocol Amendment 4, dated 13 Dec 2019, provided the following primary and key revisions. All study participants entered the study prior to the date of amendment. The primary purpose of this substantial amendment was to extend the treatment of the study participants and have LCM available for the study participants till the main approvals for an extended PGTCS indication was obtained. UCB sought to obtain the approvals in first instance in US, EU, and Japan. In addition, primary generalized tonic-clonic seizures was globally changed to PGTCS.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: An Open-label, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of study participants with treatment-emergent adverse events (TEAEs) over the duration of the Treatment Period

Primary: Number of study participants with treatment-emergent adverse events (TEAEs) over the duration of the Treatment Period

Primary: Number of study participants with an increase of greater than (>)25% to 50% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of greater than (>)25% to 50% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of up to 25% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of up to 25% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with new appearance of absence and/or myoclonic seizures during the Treatment Period

Primary: Number of study participants with new appearance of absence and/or myoclonic seizures during the Treatment Period

Primary: Number of study participants withdrawn due to TEAEs

Primary: Number of study participants withdrawn due to TEAEs

Primary: Number of study participants with an increase of >25% to 50% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >25% to 50% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >50% to 75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >50% to 75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of up to 25% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of up to 25% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >50% to 75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Number of study participants with an increase of >50% to 75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982)

Primary: Percentage of study participants with at least 50% worsening in days with absence seizures

Primary: Percentage of study participants with at least 50% worsening in days with absence seizures

Primary: Percentage of study participants with at least 50% worsening in days with myoclonic seizures

Primary: Percentage of study participants with at least 50% worsening in days with myoclonic seizures

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hemoglobin)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hemoglobin)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hematocrit)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Hematocrit)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Basophils Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Basophils Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Leukocytes)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Leukocytes)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Erythrocytes)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Erythrocytes)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Platelets)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Platelets)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Lymphocytes Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Lymphocytes Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Monocytes Absolute )

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Monocytes Absolute )

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Neutrophils Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Neutrophils Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Eosinophils Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in hematology parameters (Eosinophils Absolute)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Calcium)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Calcium)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Sodium)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Sodium)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Potassium)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Potassium)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Chloride)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Chloride)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Bicarbonate)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Bicarbonate)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Creatinine)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Creatinine)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Aspartate Aminotransferase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Aspartate Aminotransferase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in chemistry parameters (Total Bilirubin)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in chemistry parameters (Total Bilirubin)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alanine Aminotransferase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alanine Aminotransferase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alkaline Phosphatase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Alkaline Phosphatase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Gamma Glutamyl Transferase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Gamma Glutamyl Transferase)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Glucose)

Secondary: Percentage of study participants with treatment-emergent marked abnormalities (TEMAs) in serum chemistry parameters (Glucose)

Clinical Trial Results:
An Open-label, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy