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

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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Lacosamide Tablet; Drug: Lacosamide Oral Solution

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Chatswood, Australia
    • Ep0012 980
  • Heidelberg, Australia
    • Ep0012 985
  • Melbourne, Australia
    • Ep0012 986
  • Parkville, Australia
    • Ep0012 981
• Brazil
  • Curitiba, Brazil
    • Ep0012 181
  • Florianopolis, Brazil
    • Ep0012 180
  • Passo Fundo, Brazil
    • Ep0012 186
  • Porto Alegre, Brazil
    • Ep0012 185
  • Rio de Janeiro, Brazil
    • Ep0012 188
  • Sao Paulo, Brazil
    • Ep0012 183
• Bulgaria
  • Blagoevgrad, Bulgaria
    • Ep0012 500
  • Sofia, Bulgaria
    • Ep0012 501
• China
  • Beijing, China
    • Ep0012 971
  • Changchun, China
    • Ep0012 976
  • Shanghai, China
    • Ep0012 972
• Czechia
  • Ostrava- Poruba, Czechia
    • Ep0012 550
  • Prague, Czechia
    • Ep0012 553
  • Praha 11, Czechia
    • Ep0012 556
  • Zlin, Czechia
    • Ep0012 552
• France
  • Bron Cedex, France
    • Ep0012 255
  • Lille Cedex, France
    • Ep0012 252
  • Nancy, France
    • Ep0012 251
• Germany
  • Erlangen, Germany
    • Ep0012 303
  • Freiburg, Germany
    • Ep0012 314
  • Marburg, Germany
    • Ep0012 311
• Hungary
  • Budapest, Hungary
    • Ep0012 600
  • Szeged, Hungary
    • Ep0012 603
• Israel
  • Rehovot, Israel
    • Ep0012 850
  • Tel Hashomer, Israel
    • Ep0012 851
• Italy
  • Torino, Italy
    • Ep0012 351
• Japan
  • Fukuoka-shi, Japan
    • Ep0012 906
  • Gifu, Japan
    • Ep0012 910
  • Hamamatsu, Japan
    • Ep0012 903
  • Hiroshima, Japan
    • Ep0012 902
  • Kagoshima-city, Japan
    • Ep0012 912
  • Kodaira-city, Japan
    • Ep0012 914
  • Kokubunji-shi, Japan
    • Ep0012 909
  • Niigata-city, Japan
    • Ep0012 901
  • Omura-shi, Japan
    • Ep0012 911
  • Sapporo-city, Japan
    • Ep0012 900
  • Shinjuku-ku, Japan
    • Ep0012 908
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Ep0012 940
  • Seoul, Korea, Republic of
    • Ep0012 941
  • Seoul, Korea, Republic of
    • Ep0012 944
• Mexico
  • Guadalajara, Mexico
    • Ep0012 161
• Poland
  • Czestochowa, Poland
    • Ep0012 657
  • Gdansk, Poland
    • Ep0012 655
  • Gliwice, Poland
    • Ep0012 652
  • Katowice, Poland
    • Ep0012 651
  • Katowice, Poland
    • Ep0012 653
  • Katowice, Poland
    • Ep0012 654
  • Tyniec Maly, Poland
    • Ep0012 656
  • Warszawa, Poland
    • Ep0012 650
  • Warszawa, Poland
    • Ep0012 659
• Portugal
  • Lisboa, Portugal
    • Ep0012 451
• Romania
  • Iasi, Romania
    • Ep0012 704
  • Timisoara, Romania
    • Ep0012 700
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Ep0012 757
  • Kazan, Russian Federation
    • Ep0012 750
  • Pyatigorsk, Russian Federation
    • Ep0012 758
  • Saint Petersburg, Russian Federation
    • Ep0012 756
  • Samara, Russian Federation
    • Ep0012 752
  • St. Petersburg, Russian Federation
    • Ep0012 755
• Slovakia
  • Bardejov, Slovakia
    • Ep0012 821
  • Hlohovec, Slovakia
    • Ep0012 823
• Spain
  • Barcelona, Spain
    • Ep0012 402
  • Cordoba, Spain
    • Ep0012 406
  • Madrid, Spain
    • Ep0012 407
  • Sevilla, Spain
    • Ep0012 403
• Taiwan
  • Taichung, Taiwan
    • Ep0012 961
  • Taipei, Taiwan
    • Ep0012 960
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • EP0012 5
  • California
    • Santa Monica, California, United States, 90404
      • EP0012 8
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Ep0012 31
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Ep0012 42
    • Panama City, Florida, United States, 32405
      • Ep0012 13
    • Port Charlotte, Florida, United States, 33952
      • EP0012 2
  • Idaho
    • Boise, Idaho, United States, 83702
      • Ep0012 15
  • Illinois
    • Peoria, Illinois, United States, 61637
      • Ep0012 21
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Ep0012 25
  • New York
    • New York, New York, United States, 10016
      • Ep0012 43
  • Texas
    • Austin, Texas, United States, 78758
      • Ep0012 53
    • Greenville, Texas, United States, 75401
      • Ep0012 50
    • Houston, Texas, United States, 77005
      • Ep0012 34
    • San Antonio, Texas, United States, 78229
      • Ep0012 38
  • Washington
    • Renton, Washington, United States, 98057
      • Ep0012 27
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Ep0012 23

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lacosamide; Start dose SP0982 completers at V1: LCM 10 mg/kg/day for pediatric subjects weighing <30 kg; LCM 8 mg/kg/day for pediatric subjects weighing ≥ 30kg to <50 kg; LCM 400 mg/day (200 mg bid) for adult subjects (≥18 years of age) or pediatric subjects weighing ≥50 kg SP0982 Baseline failures at V1: LCM 2 mg/kg/day for pediatric subjects weighing <50 kg; LCM 100 mg/day (50 mg bid) for adult subjects (≥18 years of age) or pediatric subjects weighing ≥50 kg Oral solution (pediatric subjects <50 kg): Minimum LCM dose: 4 mg/kg/day; Maximum LCM dose: 12 mg/kg/day Tablets (pediatric subjects ≥50kg): Minimum LCM dose: 200 mg/day; Minimum LCM dose: 600 mg/day Tablets (adult subjects): Minimum LCM dose: 200 mg/day; Maximum LCM dose: 800 mg/day

Drug: Lacosamide Tablet; Active substance: Lacosamide; Pharmaceutical form: Tablet; Concentration: 50 mg and 100 mg; Route of Administration: Oral administration; Other Names: Vimpat; LCM; Drug: Lacosamide Oral Solution; Active substance: Lacosamide; Pharmaceutical form: Oral solution; Concentration: 10 mg/ml; Route of Administration: Oral administration; Other Names: Vimpat; LCM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants With Treatment-emergent Adverse Events (TEAEs) Over the Duration of the Treatment Period	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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hemoglobin)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hematocrit)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Platelets)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Erythrocytes)	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).	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Leukocytes)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Basophils Absolute)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Eosinophils Absolute)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Lymphocytes Absolute)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Monocytes Absolute )	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Neutrophils Absolute)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Calcium)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Sodium)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Potassium)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Chloride)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Bicarbonate)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Creatinine)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Aspartate Aminotransferase)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alanine Aminotransferase)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Chemistry Parameters (Total Bilirubin)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alkaline Phosphatase)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Gamma Glutamyl Transferase)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Glucose)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Albumin)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Total Protein)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Phosphate)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead Electrocardiogram (ECG) Parameter (QT Interval)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QTc(F) Interval)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QTc(B) Interval)	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.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (PR Interval)	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).	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QRS Interval)	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).	During the study (up to approximately 5 years)
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).	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Pulse Rate)	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).	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Systolic Blood Pressure)	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'.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Diastolic Blood Pressure)	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'.	During the study (up to approximately 5 years)
Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Body Weight)	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).	During the study (up to approximately 5 years)
Percent Change in Primary Generalized Tonic-clonic Seizure (PGTCS) Frequency Per 28 Days From Combined Baseline	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.	From Combined Baseline until end of Treatment Period (up to approximately 5 years)

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES, Inc.
• Investigators: Study Director: UCB Cares, 001 844 599 2273

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2015
• Primary Completion (Actual): March 30, 2023
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: March 31, 2015
• First Submitted That Met QC Criteria: March 31, 2015
• First Posted (Estimated): April 3, 2015

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Epilepsy; Children; Adults; Lacosamide; Vimpat; Primary Generalized Tonic Clonic seizures; Idiopathic Generalized Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: EP0012; 2012-001770-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No