Safety and Efficacy of Lacosamide as Additional Therapy in Patients Suffering From Epileptic Tonic-Clonic Seizures

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02408549

Acronym

VALUE

Enrollment

239

Registered

2015-04-03

Start date

2015-08-03

Completion date

2023-03-30

Last updated

2023-12-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Epilepsy

Keywords

Lacosamide, Vimpat, Epilepsy, Children, Primary Generalized Tonic Clonic seizures, Idiopathic Generalized Epilepsy, Adults

Brief summary

Assessment of long-term safety and efficacy of oral lacosamide (LCM) as an adjunctive therapy for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in subjects \>= 4 years of age with idiopathic generalized epilepsy (IGE). This study will enroll subjects from the LCM SP0982 \[NCT02408523\] study.

Interventions

DRUGLacosamide Tablet

* Active substance: Lacosamide * Pharmaceutical form: Tablet * Concentration: 50 mg and 100 mg * Route of Administration: Oral administration

DRUGLacosamide Oral Solution

* Active substance: Lacosamide * Pharmaceutical form: Oral solution * Concentration: 10 mg/ml * Route of Administration: Oral administration

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

4 Years to No maximum

Healthy volunteers

Inclusion criteria

\- Subject must have completed or be an eligible Baseline failure from the parent study (SP0982 \[NCT02408523\]). Note: Other subjects screened for SP0982 may be considered for roll-over to EP0012 if the investigator considers that the subject could benefit from treatment with open-label lacosamide (LCM) and based on prior discussion with and approval from the UCB Study Physician or representative

Exclusion criteria

* Subject is receiving any investigational drugs or using any experimental devices in addition to lacosamide (LCM) * Subject meets the withdrawal criteria for SP0982 or is experiencing an ongoing serious adverse event (SAE) * Subject has an active suicidal ideation as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Since Last Visit version of the Columbia-Suicide Severity Rating Scale (C-SSRS) * Subject has \>=2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or \>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are \>ULN and \<1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin \<35%). For all subjects who entered EP0012 directly with a Baseline result \>ULN for ALT, AST, ALP, or total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report form (eCRF). Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation.

Design outcomes

Primary

Measure	Time frame	Description
Number of Study Participants With Treatment-emergent Adverse Events (TEAEs) Over the Duration of the Treatment Period	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)	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.
Number of Study Participants Withdrawn Due to TEAEs	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)	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.
Number of Study Participants With New Appearance of Absence and/or Myoclonic Seizures During the Treatment Period	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
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)	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period	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.
Percentage of Study Participants With at Least 50% Worsening in Days With Absence Seizures	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)	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.
Percentage of Study Participants With at Least 50% Worsening in Days With Myoclonic Seizures	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)	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.

Secondary

Measure	Time frame	Description
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Chloride)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Bicarbonate)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Creatinine)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Aspartate Aminotransferase)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alanine Aminotransferase)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Chemistry Parameters (Total Bilirubin)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alkaline Phosphatase)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Gamma Glutamyl Transferase)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Glucose)	During the study (up to approximately 5 years)	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 Baseline. 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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Albumin)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Total Protein)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Phosphate)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead Electrocardiogram (ECG) Parameter (QT Interval)	During the study (up to approximately 5 years)	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 Baseline. 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 Baseline' (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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QTc(F) Interval)	During the study (up to approximately 5 years)	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 the Treatment Period but not present at Baseline. For the age range '3 years -\<12 years' and '\>=12 years- \<17 years', the abnormality criteria were from '\>440 ms' (Abn A) and '\>15% increase from Baseline' 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 Baseline' value (Abn F). The abnormality in QTc(F) 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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QTc(B) Interval)	During the study (up to approximately 5 years)	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 the Treatment Period but not present at Baseline. For the age range '3 years -\<12 years' and '\>=12 years- \<17 years', the abnormality criteria were '\>450 ms' (Abn A) and '\>15% increase from Baseline' 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 Baseline' 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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (PR Interval)	During the study (up to approximately 5 years)	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 Baseline. For the age range, '3 years -\<12 years', the abnormality criteria were '\>180 ms' (Abn A) and '\>25% increase from Baseline' value (Abn B). For the age range, '\>=12 years - \<17 years', the abnormality criteria were '\>200 ms' (Abn C) and '\>25% increase from Baseline' 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).
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QRS Interval)	During the study (up to approximately 5 years)	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 Baseline. For the age range, '3 years -\<12 years', the abnormality criteria were '\>100 ms' (Abn A) and '\>25% increase from Baseline' value (Abn B). For the age range, '\>=12 years - \<17 years', the abnormality criteria were '\>110 ms' (Abn C) and '\>25% increase from Baseline' (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).
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hemoglobin)	During the study (up to approximately 5 years)	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 Baseline. 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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Pulse Rate)	During the study (up to approximately 5 years)	TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA vital signs results of Pulse rate 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 bpm' (Low) and '\>130 bpm' (High). For the age range, '12 years - \<17 years', the abnormality criteria were '\<=50 bpm' (Low) and '\>=120 bpm' (High). For the age range, '\>=17 years', the abnormality criteria were '\<=50 bpm and a decrease from Baseline of \>=15 bpm' (Low A), '\>=120 bpm and an increase from Baseline of \>=15 bpm' (High A), '\<60 bpm' (Low B) and '\>100 bpm' (High B). The 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).
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Systolic Blood Pressure)	During the study (up to approximately 5 years)	TEMA values of Systolic Blood Pressure (BP) results 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 '\<80 millimeters of mercury (mmHg)' (Low) and '\>140 mmHg' (High). For the age range, '\>=12 years - \<17 years', the abnormality criteria were '\<90 mmHg' (Low) and '\>160 mmHg' (High). For the age range, '\>=17 years', the abnormality criteria were '\<=90 mmHg and decrease from Baseline of \>=20 mmHg' (Low A), '\>=180 mmHg and increase from Baseline 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'.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Diastolic Blood Pressure)	During the study (up to approximately 5 years)	TEMA values of Diastolic BP results were those that are observed post- BL during the Treatment Period but not present at Baseline. 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 Baseline of \>=15 mmHg' (Low A), '\>=105 mmHg and increase from Baseline 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'.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Body Weight)	During the study (up to approximately 5 years)	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).
Percent Change in Primary Generalized Tonic-clonic Seizure (PGTCS) Frequency Per 28 Days From Combined Baseline	From Combined Baseline until end of Treatment Period (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (Heart Rate Interval)	During the study (up to approximately 5 years)	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).
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hematocrit)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Platelets)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Erythrocytes)	During the study (up to approximately 5 years)	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).
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Leukocytes)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Basophils Absolute)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Eosinophils Absolute)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Lymphocytes Absolute)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Monocytes Absolute )	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Neutrophils Absolute)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Calcium)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Sodium)	During the study (up to approximately 5 years)	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.
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Potassium)	During the study (up to approximately 5 years)	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.

Countries

Australia, Brazil, Bulgaria, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, United States

Participant flow

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.

Pre-assignment 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.

Participants by arm

Arm	Count
All Participants (Lacosamide) 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.	239
Total	239

Arm

Count

All Participants (Lacosamide)

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.

239

Total

239

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	15
Overall Study	Consent withdrawn	30
Overall Study	Death	4
Overall Study	Lack of Efficacy	17
Overall Study	Lost to Follow-up	6
Overall Study	Neurology research program closing at site	1
Overall Study	Pregnancy	1
Overall Study	Protocol Violation	4
Overall Study	Site closure	1
Overall Study	Study terminated at site	1
Overall Study	Subject moved to another place, far from site	1
Overall Study	Withdrawal of consent due to business trip	1

Baseline characteristics

Characteristic	All Participants (Lacosamide)
Age, Continuous	27.9 years STANDARD_DEVIATION 12.6
Age, Customized 12-<18 years	28 Participants
Age, Customized 18-<65 years	194 Participants
Age, Customized ≥4-<12 years	16 Participants
Age, Customized ≥65 years	1 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	1 Participants
Race/Ethnicity, Customized Asian	48 Participants
Race/Ethnicity, Customized Black	4 Participants
Race/Ethnicity, Customized Hispanic or Latino	28 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	211 Participants
Race/Ethnicity, Customized Other/Mixed	8 Participants
Race/Ethnicity, Customized White	178 Participants
Sex: Female, Male Female	134 Participants
Sex: Female, Male Male	105 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	4 / 239
other Total, other adverse events	176 / 239
serious Total, serious adverse events	54 / 239

Outcome results

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)

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.

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

Population: 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).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	1 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	0 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	1 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	0 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	2 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	1 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	5 Participants

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)

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	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)	4 Participants

Primary

Number of Study Participants Withdrawn Due to TEAEs

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.

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

Population: The Safety Set included all study participants who received at least 1 dose of IMP during this study.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	Number of Study Participants Withdrawn Due to TEAEs	19 Participants

Primary

Number of Study Participants With New Appearance of Absence and/or Myoclonic Seizures During the Treatment Period

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.

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

Population: The Safety Set included all study participants who received at least 1 dose of IMP during this study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	Number of Study Participants With New Appearance of Absence and/or Myoclonic Seizures During the Treatment Period	Absence seizures	3 Participants
All Participants (Lacosamide)	Number of Study Participants With New Appearance of Absence and/or Myoclonic Seizures During the Treatment Period	Myoclonic seizures	5 Participants

Primary

Number of Study Participants With Treatment-emergent Adverse Events (TEAEs) Over the Duration of the Treatment Period

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

Population: The Safety Set included all study participants who received at least 1 dose of IMP during this study.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
All Participants (Lacosamide)	Number of Study Participants With Treatment-emergent Adverse Events (TEAEs) Over the Duration of the Treatment Period	222 Participants

Primary

Percentage of Study Participants With at Least 50% Worsening in Days With Absence Seizures

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.

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

Arm	Measure	Value (NUMBER)
All Participants (Lacosamide)	Percentage of Study Participants With at Least 50% Worsening in Days With Absence Seizures	0 percentage of participants

Primary

Percentage of Study Participants With at Least 50% Worsening in Days With Myoclonic Seizures

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.

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

Arm	Measure	Value (NUMBER)
All Participants (Lacosamide)	Percentage of Study Participants With at Least 50% Worsening in Days With Myoclonic Seizures	3.2 percentage of participants

Secondary

Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (Heart Rate Interval)

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).