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

Epilepsy Clinical Trial

— VALUE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02408549
• Other study ID #: EP0012
• Secondary ID: 2012-001770-29
• Status: Completed
• Phase: Phase 3
• Start date: August 3, 2015
• Est. completion date: March 30, 2023

Study information

• Verified date: November 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 239
• Est. completion date: March 30, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Lacosamide Tablet
Active substance: Lacosamide Pharmaceutical form: Tablet Concentration: 50 mg and 100 mg Route of Administration: Oral administration
• Lacosamide Oral Solution
Active substance: Lacosamide Pharmaceutical form: Oral solution Concentration: 10 mg/ml Route of Administration: Oral administration

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
UCB BIOSCIENCES, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Bulgaria,  China,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
Primary	Number of Study Participants With an Increase of Greater Than (>)25% to 50% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982)	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
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
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.	From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
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).	During the study (up to approximately 5 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)