A 12-Month Study To Evaluate The Safety And Tolerability Of Pregabalin As Add-On Therapy In Pediatric Subjects 1 Month To 16 Years Of Age With Partial Onset Seizures And Pediatric And Adult Subjects 5 To 65 Years Of Age With Primary Generalized Tonic-Clonic Seizures

Epilepsy, Partial Seizures Clinical Trial

Official title:

A 12-MONTH OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND TOLERABILITY OF PREGABALIN AS ADJUNCTIVE THERAPY IN PEDIATRIC SUBJECTS 1 MONTH TO 16 YEARS OF AGE WITH PARTIAL ONSET SEIZURES AND PEDIATRIC AND ADULT SUBJECTS 5 TO 65 YEARS OF AGE WITH PRIMARY GENERALIZED TONIC-CLONIC SEIZURES

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01463306
• Other study ID #: A0081106
• Secondary ID: 2011-001412-65
• Status: Completed
• Phase: Phase 3
• Start date: February 21, 2012
• Est. completion date: August 22, 2019

Study information

• Verified date: January 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study A0081106 is a 12-month open-label study to evaluate the long term safety and tolerability of pregabalin as add-on therapy in pediatric subjects 1 month to 16 years of age with partial onset seizures and pediatric and adult subjects 5 to 65 years of age with primary generalized tonic-clonic seizures. Pregabalin will be administered in equally divided daily doses for 1 year, in either capsule or liquid oral formulation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 605
• Est. completion date: August 22, 2019
• Est. primary completion date: August 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 66 Years

Eligibility

Inclusion Criteria:

• Subjects and/or parent(s)/legally acceptable representative must be considered willing and able to sign consent, and complete daily dosing and seizure diaries and complete all scheduled visits.
• Male and female epilepsy subjects, 1 month to 65 years of age inclusive on the date of the Screening Visit.
• Diagnosis of epilepsy with seizures classified as simple partial, complex partial, or partial becoming secondarily generalized, or primary generalized tonic-clonic seizures according to the International League Against Epilepsy (ILAE 2010) Diagnosis Criteria.
• Partial onset seizure subjects must have had an average of at least 3 seizures per 28 day period in the 3 months prior to screening.
• Currently receiving a stable dose of 1 to 3 antiepileptic drugs (stable within 28 days prior to screening).

Exclusion Criteria:

• Lennox-Gastaut syndrome, Infantile Spasms, Absence seizures, BECT (Benign Epilepsy with Centrotemporal Spikes), and Dravet syndrome,
• A current diagnosis of febrile seizures or any febrile seizure within 1 year of screening.
• Status epilepticus within 1 year prior to visit 1.
• Seizures related to drugs, alcohol, or acute medical illness.
• Progressive structural CNS lesion or a progressive encephalopathy.

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Epilepsy, Partial Seizures
• Epilepsy, Primary Generalized Tonic-Clonic Seizures
• Seizures

Intervention

Drug:
• Pregabalin
Pregabalin administered as either capsule or liquid oral formulations. Subjects <4 years of age at Visit 1 will receive study medication 3 times daily (TID) in equally divided doses. Subjects who are =4 years of age at Visit 1 will receive study medication twice daily (BID) in equally divided doses. Children less than 17 years of age will receive from 2.5 mg/kg/day to 10.0 mg/kg/day (maximum 600 mg/day. Adults 17 and older will receive from 150 mg/day to 600 mg/day.

Locations

Country	Name	City	State
Belarus	GU Republican Scientific and Practical Center Mother and Child	Minsk
Belarus	UZ Vitebsk Regional Childrens Clinical Centre	Vitebsk
Belarus	UZ Vitebsk Regional Childrens Clinical Centre	Vitebsk
Belgium	UZ Brussel - Campus Jette - Pediatric Neurology	Brussel	Bruxelles Capitale
Belgium	Hopital Universitaire Des Enfants Reine Fabiola	Brussels	Brussels-capital
Belgium	Hospital Erasme	Brussels	Brussels-capital
Bosnia and Herzegovina	University Clinical Hospital Mostar	Mostar	Herzegovina-neretva Canton
Bosnia and Herzegovina	Public Health Institution Hospital "Dr. Mladen Stojanovic"	Prijedor	Republika Srpska
Bosnia and Herzegovina	University Clinical Center Sarajevo	Sarajevo	Canton Sarajevo, Bosnia AND Herzegovina
Bulgaria	"Multiprofile Hospital for Active Treatment Puls" AD	Blagoevgrad
Bulgaria	UMHAT Dr. Georgi Stranski Ltd.	Pleven
Bulgaria	MHAT Central Onco Hospital OOD	Plovdiv
Bulgaria	UMHAT "Sveti Georgi" Ltd., Pediatric Clinic	Plovdiv
Bulgaria	DCC Sveta Anna - Sofia\ Neurological room	Sofia
Bulgaria	MHATNP Sveti Naum EAD	Sofia
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	Children's Hospital of Fudan University	Shanghai	Shanghai
China	Shanghai Huashan Hospital	Shanghai	Shanghai
Czechia	Fakultni nemocnice Brno - Detska nemocnice	Brno - Cerna Pole
Czechia	Fakultni nemocnice v Motole	Praha 5
France	Hopital Raymond Poincare	Garches
France	CHRU de Rennes - Hopital Pontchaillou	Rennes
France	Hopitaux Universitaire de Strasbourg - Hopital Hautepierre	Strasbourg
Germany	Universitaetsklinikum Jena	Jena	Thueringen
Greece	General Children's Hospital of Athens "P&A Kyriakou"	Athens
Greece	General Children's Hospital Penteli	Athens
Hungary	Dr. Kenessey Albert Kórház és Rendelointézet	Balassagyarmat
Hungary	Heim Pal Gyermekkorhaz, Neurologiai Osztaly	Budapest
Hungary	Magyarorszagi Reformatus Egyhaz Bethesda Gyermekkorhaz, Gyermekneurologia	Budapest
Hungary	Semmelweis Egyetem, I. Sz. Gyermekgyogyaszati Klinika/	Budapest
Hungary	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak	Budapest
Hungary	Szent Margit Korhaz	Budapest
Hungary	Pest Megyei Flor Ferenc Korhaz, Neurologiai Osztaly	Kistarcsa
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs
India	Getwell Hospital and Research Institute	Dhantoli, Nagpur	Maharashtra
India	Mangala Hospital & Mangala Kidney Foundation	Mangalore	Karnataka
India	KEM Hospital Research Centre	Pune	Maharashtra
Israel	Bnai Zion Medical Center	Haifa
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Pharmacy of Tel Aviv Sourasky Medical Center	Tel-Aviv
Italy	A.O.U. Ospedali Riuniti di Ancona - Presidio Ospedaliero G. Salesi - S.O.D. Farmacia	Ancona
Italy	A.O.U. Ospedali Riuniti di Ancona Presidio Ospedaliero G. Salesi	Ancona
Italy	Azienda Ospedaliero-Universitaria Meyer	Firenze
Italy	Fondazione Istituto Neurologico Nazionale Casimiro Mondino, IRCCS	Pavia
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Lebanon	American University of Beirut Medical Center	Beirut
Lebanon	Saint George Hospital - University Medical Center	Beirut
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh	Perak
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Montenegro	Pzu Neuron	Bijelo Polje
Philippines	Cebu Doctors' University Hospital	Cebu City	Cebu
Philippines	Perpetual Succour Hospital	Cebu City,
Philippines	Philippine Children's Medical Center	Diliman, Quezon City
Philippines	Metropolitan Medical Center	Manila
Philippines	University of Santo Tomas Hospital	Manila
Philippines	Manila Doctors Hospital	Manila,
Philippines	Capitol Medical Center Inc.	Quezon City
Philippines	St. Luke's Medical Center	Quezon City
Poland	COPERNICUS Podmiot Leczniczy Sp z o.o.	Gdansk
Poland	Klinika Neurologii Rozwojowej	Gdansk
Poland	Nzoz Novo Med	Katowice
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS, Lech Szczechowski	Katowice
Poland	Gabinet lekarski Neurologii I Leczenia padaczki	Kielce
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "HIPOKRATES-II" Sp. z o.o.	Krakow
Poland	Instytut Medycyny Wsi im. Witolda Chodzki w Lublinie	Lublin
Poland	Katedra i Klinika Neurologii Wieku Rozwojowego	Poznan
Poland	NZOZ "IGNIS" Dr. n. med. Alicja Lobinska	Swidnik
Poland	Oddzial Neurologii Dzieciecej, Dolnoslaski Szpital Specjalistyczny im.T. Marciniaka,	Wroclaw
Romania	Spitalul clinic de copii Dr. Victor Gomoiu	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"	Bucuresti
Romania	Spitalul Clinic de Urgente pentru Copii "Sf. Maria"	Iasi
Romania	Spitalul de Psihiatrie Dr. Ghe. Preda	Sibiu
Romania	Centrul Medical Dr. Bacos Cosma	Timisoara
Russian Federation	TSBHI City Hospital No. 5 of Barnaul	Barnaul
Russian Federation	FSFEI HE N.I. Pirogov RNRMU of Minzdrav of Russia	Moscow
Russian Federation	FSFEI HE N.I. Pirogov RNRMU of Minzdrav of Russia	Moscow
Russian Federation	Non-state Healthcare Institution	Moscow
Russian Federation	Nizhmedklinika	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	Perm State Medical University n. a. acad. E.A. Vagner	Perm	Permskiy KRAY
Russian Federation	Perm State Medical University n. a. acad. E.A. Vagner	Perm
Russian Federation	SPHI Leningrad Regional Psychoneurological Dispensary	Pgt. Roshchino	Leningrad Region
Russian Federation	State Budgetary Healthcare Institution of Stavropol region	Pyatigorsk	Stavropol Region
Russian Federation	FSBI V.M. Bekhterev National Research Medical Center	Saint Petersburg
Russian Federation	SBHI of Saint Petersburg Psychoneurological Dispensary #5	Saint Petersburg
Russian Federation	SBHI of Saint Petersburg Psychoneurological Dispensary #5	Saint Petersburg
Russian Federation	LLC Medical Technologies	Saint-Petersburg
Russian Federation	LLC Medical Technologies	Saint-Petersburg
Russian Federation	SPHI Leningrad Regional Psychoneurological Dispensary	Saint-Petersburg
Russian Federation	GBOU VPO "Smolensk State Medical University"	Smolensk
Russian Federation	Regional State Budgetary Institution of Ministry of Health	Smolensk
Russian Federation	RSBHI Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	MAI Children's City Clinical Hospital No 9	Yekaterinburg
Serbia	Mother and Child Healthcare Institute Dr Vukan Cupic	Belgrade
Serbia	University Children's Hospital Belgrade	Belgrade
Serbia	Clinical Center of Kragujevac	Kragujevac
Serbia	Institute for Child and Youth Healthcare of Vojvodina	Novi Sad	Vojvodina
Singapore	KK Women's and Children's Hospital	Singapore
Singapore	National University Hospital	Singapore
Slovakia	Neurologicka ambulancia MUDr. Eva Gasparova	Hlohovec
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch	Kaohsiung,
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Siriraj Hospital, Mahidol University, Faculty of Medicine	Bangkoknoi	Bangkok
Thailand	Phramongkutklao Hospital, Neurology Unit,	Ratchathevee, Bangkok
Turkey	Hacettepe University Medical Faculty	Ankara	Ankara/sihhiye
Turkey	Eskisehir Osmangazi University Medical Faculty	Eskisehir	Meselik Campus
Turkey	Behcet Uz Children Disease and Surgery Training and Research Hospital	Izmir	Konak
Turkey	Dokuz Eylül University medical Faculty Internal Medicine Disease	Izmir
Turkey	Ege University Medical Faculty Department of Pediatrics Health and Diseases,	Izmir	Bornova/izmir
Turkey	Izmir Tepecik Training and Research Hospital	Izmir	Konak Turkey
Turkey	Karadeniz Technical University Faculty of Medicine Farabi Hospital	Trabzon	Farabi
Ukraine	Komunalnyi zaklad "Dnipropetrovska dytiacha miska klinichna likarnia #5"	Dnipro
Ukraine	Komunalnyi zaklad "Dnipropetrovska oblasna dytiacha klinichna likarnia"	Dnipropetrovsk
Ukraine	Ivano-Frankivska oblasna dytiacha klinichna likarnia	Ivano-Frankivsk
Ukraine	Derzhavna ustanova "Instytut nevrolohii, psykhiatrii ta narkolohii	Kharkiv
Ukraine	Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasna klinichna psykhiatrychna li	Kharkiv
Ukraine	Derzhavnyi zaklad "Ukrainskyi medychnyi tsentr reabilitatsii ditei z orhanichnym urazhenniam	Kyiv
Ukraine	Komunalne nekomertsiine pidpryiemstvo Lvivskoi oblasnoi rady Lvivska oblasna klinichna likarnia, Lv	Lviv
Ukraine	Komunalna ustanova "Odeskyi oblasnyi medychnyi tsentr psykhichnoho zdorovia"	Odesa
Ukraine	Komunalne nekomertsiine pidpryiemstvo "Odeskyi oblasnyi medychnyi tsentr psykhichnoho zdoroviaa"	Odesa
Ukraine	KU "Odeska oblasna dytiacha klinichna likarnia"	Odesa
Ukraine	Komunalna ustanova "Odeska oblasna psykhiatrychna likarnia No2"	S. Oleksandrivka, Kominternivskyi R-n, Odeska Obl.
Ukraine	Oblasnyi klinichnyi tsentr neirokhirurhii ta nevrolohii, viddilennia neirokhirurhii No2	Uzhgorod
Ukraine	Komunalna ustanova "Miska klinichna likarnia #2", nevrolohichne viddilennia	Zaporizhzhia
United Kingdom	The Barberry National Centre for Mental Health	Birmingham	WEST Midlands
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	Akron Children's Hospital	Akron	Ohio
United States	Ohio Clinical Research Partners, LLC	Canton	Ohio
United States	Dallas Pediatric Neurology Associates	Dallas	Texas
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Josephson Wallack Munshower Neurology P.C.	Indianapolis	Indiana
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	University of Louisville Physicians	Louisville	Kentucky
United States	Axcess Medical Research	Loxahatchee Groves	Florida
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Laszlo J. Mate, M.D., P.A.	North Palm Beach	Florida
United States	Pediatric Epilepsy Center Of Central Florida	Orlando	Florida
United States	Pediatric Neurology, PA	Orlando	Florida
United States	The children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rainier Clinical Research Center, Inc.	Renton	Washington
United States	Road Runner Research, Ltd.	San Antonio	Texas
United States	Tallahassee Neurological Clinic	Tallahassee	Florida
United States	Pediatric Epilepsy and Neurology Specialists, PA	Tampa	Florida
United States	Center for Neurosciences	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  China,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Lebanon,  Malaysia,  Montenegro,  Philippines,  Poland,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (AEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Related AEs and Treatment Related SAEs	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent are events between first dose of study drug and up to 28 days after last dose of study drug (up to 13 months) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.	Baseline (Day 1) up to 13 Months
Primary	Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings up to 12 Months	Physical examination assessed: general appearance, dermatological, head and eyes, ears, nose, mouth, and throat, pulmonary, cardiovascular, abdominal, genitourinary (optional), lymphatic, musculoskeletal/extremities. Neurological examination assessed: level of consciousness, mental status, cranial nerve assessment, muscle strength and tone, reflexes, pin prick and vibratory sensation, coordination and gait. Investigator judged clinically significant change from baseline in physical and neurological examination findings.	Baseline up to 12 Months
Primary	Number of Participants Meeting Pre-defined Criteria for Vital Signs Abnormalities	Pre-defined criteria of vital signs abnormalities: maximum (max.) increase or decrease from baseline in sitting/supine systolic blood pressure (SBP) >=30 millimeter of mercury (mmHg); maximum increase or decrease from baseline in sitting/supine diastolic blood pressure (DBP) >=20 mmHg.	Baseline up to 12 months
Primary	Number of Participants With Tanner Staging Evaluation at Baseline	Tanner stage defines physical measurements of development based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males), with values ranging from stage 1 (pre-pubertal characteristics) to stage 5 (adult or mature characteristics).	Baseline (Day 1)
Primary	Number of Participants With Tanner Staging Evaluation at Month 12	Tanner stage defines physical measurements of development based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males), with values ranging from stage 1 (pre-pubertal characteristics) to stage 5 (adult or mature characteristics).	Month 12
Primary	Number of Participants With >=7 Percent (%) Change From Baseline in Body Weight up to 12 Months	In this outcome measure number of participants with increase and decrease of >=7% in body weight, from baseline up to 12 months are reported.	Baseline up to 12 Months
Primary	Absolute Values for Body Height at Baseline		Baseline
Primary	Absolute Values for Body Height at Month 12		Month 12
Primary	Number of Participants With Incidence of Laboratory Abnormalities	Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit, red blood cell(RBC) count: <0.8*lower limit of normal(LLN), platelet: <0.5*LLN/greater than (>)1.75*upper limit of normal (ULN), white blood cell (WBC): <0.6*LLN/>1.5*ULN, lymphocyte, neutrophil- absolute/%:<0.8*LLN/>1.2*ULN, basophil, eosinophil, monocyte- absolute/%:>1.2*ULN; total/direct/indirect bilirubin >1.5*ULN, aspartate aminotransferase (AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:> 3.0*ULN, total protein, albumin: <0.8*LLN/>1.2*ULN; thyroxine, thyroid stimulating hormone <0.8*LLN/>1.2*ULN; cholesterol, triglycerides:> >1.3*ULN; blood urea nitrogen, creatinine:>1.3*ULN; sodium <0.95*LLN/>1.05*ULN, potassium, chloride, calcium: <0.9*LLN or >1.1*ULN; glucose <0.6*LLN/>1.5*ULN, creatine kinase>2.0*ULN; urine (specific gravity <1.003/>1.030, pH <4.5/>8, glucose, ketones, protein: >=1, WBC, RBC:>=20, bacteria >20, hyaline casts/casts >1); prothrombin (PT), PT international ratio>1.1*ULN.	Baseline up to 12 Months
Primary	Number of Participants With Maximum Change From Baseline up to 12 Months in 12-Lead Electrocardiogram (ECG) Parameters	Categories for which data is reported are: 1) maximum (max) PR interval increase from baseline (IFB) (millisecond [msec]) percent change (PctChg) >=25/50%; 2) maximum QRS complex increase from baseline (msec) PctChg>=50%; 3) maximum QTcB interval (Bazett's correction) increase from baseline (msec): change >=30 to <60; change >=60; 4) maximum QTcF interval (Fridericia's correction) increase from baseline (msec): change >=30 to <60; change >=60. 'PctChg>=25/50%': >= 25% increase from baseline when baseline ECG parameter is > 200 msec, and is >= 50% increase from baseline when baseline ECG parameter is non-missing and <=200 msec.	Baseline up to 12 Months
Primary	28-Days Seizure Rate at Week 1	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Week 1
Primary	28-Days Seizure Rate at Month 1	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Month 1
Primary	28-Days Seizure Rate at Month 2	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Month 2
Primary	28-Days Seizure Rate at Month 4	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Month 4
Primary	28-Days Seizure Rate at Month 6	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Month 6
Primary	28-Days Seizure Rate at Month 9	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Month 9
Primary	28-Days Seizure Rate at Month 12/Early Termination	28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.	Month 12/Early Termination
Secondary	Number of Participants With Suicidal Ideation as Per Columbia Suicide Severity Rating Scale (C-SSRS) Mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA)	Number of participants with C-CASA code 4 are reported. C-SSRS responses mapping to C-CASA suicidal ideation code 4 are as follows: "Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with any methods (not plan) without intent to act", "active suicidal ideation with some intent to act, without specific plan", "active suicidal ideation with some intent to act, without specific plan".	Baseline (Day 1), Post-baseline on Day 1 up to 12 Months
Secondary	Number of Participants With Suicidal Behavior as Per Columbia Suicide Severity Rating Scale (C-SSRS) Mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA)	Number of participants with C-CASA code 1 or 2 or 3 are reported. C-SSRS responses mapping to C-CASA suicidal behavior codes 1, 2, or 3 are as follows: (1) completed suicide; (2) suicide attempt (response of "Yes" on "actual attempt"); (3) preparatory acts toward imminent suicidal behavior ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior").	Baseline (Day 1), Post-baseline up to 12 Months
Secondary	Number of Participants as Per Reliable Change Index (RCI) Category for Cogstate Detection Task	CogState brief battery consisted of 2 tasks- detection and pediatric identification task using a laptop computer with external response buttons. Prior tasks, participants were briefed rules, given an interactive demonstration and a sufficient number of practice trials. For each task, participant responded "yes" using a response button with dominant hand. Participants had to "respond as fast and as accurately as possible." Detection task: measured simple reaction time to assess psychomotor function. Participant pressed a "YES" response key as soon as they detected an event (ie, a card turning face up presented in the center of the computer screen). A participant's RCI was calculated by dividing the change from individual baseline score by ([square root 2] times WSD), where WSD is within-subject standard deviation from Cogstate detection task normative data. Improvement in cognition when RCI <=-1.65, decline in cognition when RCI =>1.65.	Month 12
Secondary	Number of Participants as Per Reliable Change Index Category for Cogstate Pediatric Identification Task	CogState brief battery consisted of 2 tasks-detection and pediatric identification task using a laptop computer with external response buttons. Prior tasks, participants were briefed rules, given an interactive demonstration and a sufficient number of practice trials. For each task, participant responded "yes" using a response button with dominant hand. Participants had to "respond as fast and as accurately as possible." Pediatric identification task: measured choice reaction time to assess visual attention. An event (a card turning face up) occurred in center of computer screen and participant decided if event met a predefined and unchanging criterion (is the color of the card black?); answered "YES" if criterion was met. A participant's RCI was calculated by dividing the change from individual baseline score by ([square root 2] times WSD),WSD=within-subject standard deviation from Cogstate task normative data. Improvement in cognition: RCI <=-1.65, decline in cognition: RCI =>1.65.	Month 12