Partial-Onset or Primary Generalized Tonic-Clonic Seizures Clinical Trial
Official title:
An Open-Label, Multicenter Study With an Extension Phase to Evaluate the Safety, Tolerability, and Exposure-Efficacy Relationship of Perampanel Oral Suspension When Administered as an Adjunctive Therapy in Pediatric Subjects (Age 4 to Less Than 12 Years) With Inadequately Controlled Partial-Onset Seizures or Primary Generalized Tonic Clonic Seizures
| Verified date | October 2022 |
| Source | Eisai Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is an open-label, multicenter study with an Extension Phase to evaluate the safety and tolerability of perampanel oral suspension when administered as an adjunctive therapy in children (ages 4 to less than [<] 12 years) with inadequately controlled partial onset seizures (POS) or primary generalized tonic clonic (PGTC) seizures.
| Status | Completed |
| Enrollment | 180 |
| Est. completion date | December 6, 2021 |
| Est. primary completion date | February 5, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 4 Years to 12 Years |
| Eligibility | Inclusion Criteria: - Have a diagnosis of epilepsy with POS with or without secondarily generalized (SG) seizures or PGTC seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981). A diagnosis should have been established at least 6 months prior to Visit 1 by clinical history and an electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (that is, clinical history) - Male or female participant, from age 4 to <12 years at the time of informed consent/assent - Have a minimum weight of 16 kilograms (kg) (35 pounds [lb]) - Have had a brain imaging (example, magnetic resonance imaging [MRI] scan or computed tomography [CT] before Visit 1 that ruled out a progressive cause of epilepsy) - During the 12 weeks +/- 3 days (4 weeks +/- 3 days in Japan only) prior to Visit 2, participants must have equal or greater than (=>) one POS or one PGTC seizure. Only simple POS with motor signs, complex POS, and complex POS with secondary generalization are counted toward this inclusion for POS - Are currently being treated with stable doses of 1 to a maximum of 3 approved antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before to Visit 1; in the case where a new AED regimen has been initiated for a participant, the dose must be stable for at least 8 weeks prior to Visit 1. Only one EIAED (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of three AEDs is allowed (A vagal nerve stimulator [VNS] will be counted as one of the 3 allowed AEDs) Exclusion Criteria: - Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International Units per liter [IU/L] or equivalent units of ß-hCG or hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug - Females of childbearing potential who: - Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (example, total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation. If a highly effective method is not appropriate or acceptable for the participant, then the participant may use a medically effective method (example, a double barrier method such as condom plus diaphragm with spermicide) - Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from being sexually active during the study period or for 28 days after study drug discontinuation - Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation - Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before Visit 1 - Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1 - Have an unstable psychiatric diagnosis that may confound participants' ability to participate in the study or that may prevent completion of the protocol-specified tests (example, significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1, current psychotic disorder, acute mania) - Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale [C-SSRS]) in participants aged 6 and above - Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1; however, those who have previously documented "failed" epilepsy surgery will be allowed - Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments - Evidence of moderate or severe renal insufficiency as defined by estimated glomerular filtration rates (eGFRs) of 31 to <60 milliliters per minute (mL/min) and <30 mL/min, respectively - Evidence of significant active hepatic disease. Stable elevation of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) due to concomitant medication(s), will be allowed if they are less than 3 times the upper limit of normal (ULN) - Evidence of significant active hematological disease; white blood cell (WBC) count equal or less than (=<) 2500 per (/) microliter (µL) (2.50 1 constant [E]+09/liter [L]) or an absolute neutrophil count =<1000/µL (1.00 1E+09/L) - Clinically significant electrocardiogram (ECG) abnormality, including prolonged corrected QT interval (QTc) defined as greater than (>) 450 milliseconds (msec) - Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors - Multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (example, Stevens Johnson syndrome), hematological, or organ toxicity reactions. - Concomitant use of felbamate as an AED for <2 years or where the dose has not been stable for at least 8 weeks before Visit 1. Participants must not have a history of WBC count =<2500/µL, platelets below 100,000, liver function tests (LFTs) above 3 times the ULN, or other indication of hepatic or bone marrow dysfunction while receiving felbamate. If participants received felbamate in the past, it must have been discontinued 8 weeks before Visit 1 to be eligible for study participation - Concomitant use of vigabatrin: participants who took vigabatrin in the past must be off vigabatrin for at least 5 months before Visit 1 and with documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in a visual perimetry test - Concomitant use of cannabinoids - Used benzodiazepines for epilepsy during which the dose has not been stable for >4 weeks prior to Visit 1. Benzodiazepines use as rescue medication for seizure control is allowed; however, intermittent use of benzodiazepines for any other indication (example, anxiety/sleep disorders) is prohibited - A VNS implanted <5 months before Visit 1 or changes in parameter <4 weeks before Visit 1 (or thereafter during the study) - On a ketogenic diet for which the diet is not a stable regimen for at least 4 weeks before Visit 1 - History of or a concomitant medical condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study or compromise the participant's ability to safely complete the study - Have previously been exposed to perampanel in a clinical trial or by prescription for more than 2 months or discontinued for Adverse Events (AEs) - Have participated in a study involving administration of an investigational drug or device within 4 weeks before Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer - Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Facility #1 | Brussels | |
| Belgium | Facility #1 | Bruxelles | Brussels |
| Belgium | Facility #1 | La Louviere | Hainaut |
| Belgium | Facility #1 | Ottignies | Brabant Wallon |
| Belgium | Facility #1 | Pulderbos | Antwerpen |
| Canada | Facility #1 | Calgary | Alberta |
| Canada | Facility #1 | Montreal | Quebec |
| Czechia | Facility #1 | Ostrava | |
| Czechia | Facility #1 | Praha 4 | |
| France | Facility #1 | Lille Cedex | |
| France | Facility #1 | Marseille | |
| France | Facility #1 | Marseille | Bouches-du-Rhone |
| France | Facility #1 | Paris | |
| France | Facility #2 | Paris | |
| France | Facility #1 | Strasbourg | |
| France | Facility #1 | Toulouse Cedex 9 | |
| Hungary | Facility #1 | Budapest | |
| Hungary | Facility #2 | Budapest | |
| Hungary | Facility #1 | Miskolc | |
| Hungary | Facility #1 | Pecs | |
| Italy | Facility #1 | Bologna | |
| Italy | Facility #1 | Calambrone | Toscana |
| Italy | Facility #1 | Firenze | |
| Italy | Facility #1 | Mantova | Lombardia |
| Italy | Facility #1 | Milano | |
| Japan | Eisai Trial Site #1 | Fukuoka | |
| Japan | Eisai Trial Site #1 | Fukuoka-shi | |
| Japan | Eisai Trial Site #1 | Gifu | |
| Japan | Eisai Trial Site #1 | Hakodate-shi | |
| Japan | Eisai Trial Site #1 | Hamamatsu | Sizuoka |
| Japan | Eisai Trial Site #1 | Hiroshima | |
| Japan | Eisai Trial Site #1 | Izumi | |
| Japan | Eisai Trial Site #1 | Kobe | |
| Japan | Eisai Trial Site #1 | Kumamoto | |
| Japan | Eisai Trial Site #1 | Nagoya | |
| Japan | Eisai Trial Site #1 | Nara | |
| Japan | Eisai Trial Site #1 | Niigata | |
| Japan | Eisai Trial Site #1 | Okayama | |
| Japan | Eisai Trial Site #1 | Omura | |
| Japan | Eisai Trial Site #1 | Osaka | |
| Japan | Eisai Trial Site #1 | Sagamihara | |
| Japan | Eisai Trial Site #1 | Sapporo | |
| Japan | Eisai Trial Site #1 | Sapporo | Hokkaido |
| Japan | Eisai Trial Site #1 | Sendai-shi | Miyagi |
| Japan | Eisai Trial Site #1 | Shizuoka | |
| Japan | Eisai Trial Site #1 | Yamagata | |
| Japan | Eisai Trial Site #1 | Yokohama-shi | |
| Japan | Eisai Trial Site #1 | Zentsuji | Kagawa |
| Korea, Republic of | Facility #1 | Daegu | |
| Korea, Republic of | Facility #1 | Daejeon | |
| Korea, Republic of | Facility #1 | Seoul | |
| Korea, Republic of | Facility #2 | Seoul | |
| Korea, Republic of | Facility #3 | Seoul | |
| Latvia | Facility #1 | Riga | |
| Poland | Facility #1 | Gdansk | Pomorskie |
| Poland | Facility #1 | Kielce | Swietokrzyskie |
| Poland | Facility #1 | Poznan | Wielkopolskie |
| Spain | Facility #1 | Barcelona | |
| Spain | Facility #2 | Barcelona | |
| Spain | Facility #1 | Esplugues de Llobregat | Barcelona |
| Spain | Facility #1 | Madrid | |
| Spain | Facility #1 | Sevilla | |
| Spain | Facility #1 | Valencia | |
| United States | Facility #1 | Ames | Iowa |
| United States | Facility #1 | Atlanta | Georgia |
| United States | Facility #1 | Aurora | Colorado |
| United States | Facility #1 | Austin | Texas |
| United States | Facility #1 | Boise | Idaho |
| United States | Facility #1 | Brooklyn | New York |
| United States | Facility #1 | Chicago | Illinois |
| United States | Facility #1 | Cleveland | Ohio |
| United States | Facility #1 | Duluth | Minnesota |
| United States | Facility #1 | Gulf Breeze | Florida |
| United States | Facility #1 | Hackensack | New Jersey |
| United States | Facility #1 | Henderson | Nevada |
| United States | Facility #1 | Kansas City | Missouri |
| United States | Facility #1 | Lexington | Kentucky |
| United States | Facility #2 | Lexington | Kentucky |
| United States | Facility #1 | Little Rock | Arkansas |
| United States | Facility #1 | Loxahatchee Groves | Florida |
| United States | Facility #1 | Memphis | Tennessee |
| United States | Facility #1 | Milwaukee | Wisconsin |
| United States | Facility #1 | New Orleans | Louisiana |
| United States | Facility #1 | Orlando | Florida |
| United States | Facility #1 | Palo Alto | California |
| United States | Facility #1 | San Antonio | Texas |
| United States | Facility #1 | Savannah | Georgia |
| United States | Facility #1 | Tacoma | Washington |
| United States | Facility #1 | Urbana | Illinois |
| United States | Facility #1 | Voorhees | New Jersey |
| United States | Facility #1 | Wichita | Kansas |
| United States | Facility #1 | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Eisai Inc. |
United States, Belgium, Canada, Czechia, France, Hungary, Italy, Japan, Korea, Republic of, Latvia, Poland, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Participants - Core Phase and Extension Phase A of This Study | Baseline up to 4 weeks (follow up in Extension Phase A) after last dose of study drug in Extension Phase A at Week 52 (up to 56 weeks) | ||
| Primary | Percentage of Participants With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Participants- Core Phase and Extension Phase A of This Study | Baseline up to 52 weeks | ||
| Primary | Percentage of Participants With Abnormal Vital Sign Values for Total Group of Participants- Core Phase and Extension Phase A of This Study | Pre-defined criteria of vital signs abnormalities: maximum (max.) increase or decrease from baseline in sitting/supine systolic blood pressure (SBP) of greater than or equal to (>=) 20 or 40 millimeter of mercury (mmHg); maximum increase or decrease from baseline in sitting/supine diastolic blood pressure (DBP) >=10 or 20 mmHg; increase or decrease from baseline in pulse rate (number of heart beats per minute [bpm]) of >=15 or 30 bpm. Data for this outcome measure has been assessed and reported till Week 52. | Baseline up to 52 weeks | |
| Primary | Percentage of Participants With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Participants- Core Phase and Extension Phase A of This Study | Baseline up to 52 weeks | ||
| Secondary | Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL) | Seizure frequency derived from information (seizure count and type) recorded in participant diary. Seizure frequency per 28 days was calculated as number of seizures divided by number of days in interval; multiplied by 28. Due to sparse pharmacokinetic (PK) sampling in study, data of endpoint was analyzed by pooling data from other Phase II and III studies of perampanel along with data of this current study, including participants with POS or PGTC. Only data for participants taking perampanel 8 mg/day (corresponding to Cav, ss of 518 ng/mL) were reported. Participants taking perampanel 12 mg/day in studies from which data were pooled, were not included in analysis for this measure. Here, ng/mL= nanogram per milliliter. Data for this measure was calculated through model prediction; reported as "percent change" with measure type as "number" and measure dispersion as "Not applicable, NA". | Baseline, Week 23 | |
| Secondary | Overall Responder Probability For Non-Asian Participants With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel | For this outcome measure, responders were those who experienced a 50 percent (%) or greater reduction in seizure frequency per 28 days from baseline. Due to the sparse PK sampling in this study, the data of this outcome measure were pooled with data from other Phase III studies of perampanel conducted in participants with POS. "AEDs not affecting PK" refers to AEDs not affecting PK of perampanel. Data for this outcome measure has been reported for only non-Asian participants with POS per age groups. Responder probability has been reported for Cav,ss of perampanel when given along with different antiepileptic drugs (AEDs). | Baseline up to 23 weeks | |
| Secondary | Overall Responder Probability For Participants With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel | For this outcome measure, responders were those who experienced a 50% or greater reduction in seizure frequency per 28 days from baseline. Due to the sparse PK sampling in this study, the data of this outcome measure were analyzed by pooling the data from other Phase II and III studies of perampanel along with data of this current study, including participants with PGTC seizures. In this outcome measure, responder probability at different concentration values of perampanel when given with or without topiramate (an antiepileptic) has been reported. | Baseline up to 23 weeks | |
| Secondary | Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel | Due to the sparse PK sampling in this study, the data of this outcome measure were analyzed by pooling data from other Phase II and III studies of perampanel along with this current study, including participants with POS or PGTC. Data for this outcome measure have been reported in relationship with different ranges of Cav, ss of Perampanel as "number of observations" those were seizure free for up to 3 visits. The reason for using number of observations for analysis of this outcome measure was because data were available as up to 3 visits per participant and not necessarily that the participant was seizure-free on all three visits. | Baseline up to Week 23 | |
| Secondary | Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel | The ABNAS assessment measured 5 aspects of cognitive function such as fatigue, memory, concentration, motor speed, and reading. The assessment was a measure of participant-perceived cognitive effects of AEDs. This instrument was aimed at assessing participant perceived drug-related cognitive impairment. Total score ranged from 0-72. Higher scores indicate a worsening of these cognitive functions. Analysis for this outcome measure was planned to be performed via Pharmacokinetic/Pharmacodynamic (PK/PD) modelling only if a graphical relationship between perampanel exposure and change from baseline in ABNAS could be discerned. | Baseline up to Week 23 | |
| Secondary | Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Participants Aged 4 to 5 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel | The CBCL for participants with age 4 to 5 years is a questionnaire to assess behavioral and emotional problems in children as reported by the primary caregiver for the following domains activities: emotionally reactive, anxious/depressed, withdrawn, somatic complaints, internalizing, attention problems, aggressive behavior, externalizing, sleep problems. CBCL total score for participants with age 4 to 5 years ranged from 0 to 200, was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior. Analysis for this outcome measure was planned to be performed via PK/PD modelling only if a graphical relationship between perampanel exposure and change from baseline in CBCL score (participants aged 4 to 5 years) could be discerned. | Baseline up to Week 23 | |
| Secondary | Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Participants Aged Greater Than [>] 5 to <12 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel | The CBCL for participants with age >5 to <12 years is a questionnaire to assess behavioral and emotional problems in children as reported by the primary caregiver for the following domains activities: activity, social, school, total competence, anxious/depressed, withdrawn/depressed, somatic complaints, internalizing, rule-breaking behavior, aggressive behavior, externalizing, social problems, thought problems, attention problems. CBCL total score for participants with age >5 to <12 years ranged from 0 to 240, was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior. Analysis for this outcome measure was planned to be performed via PK/PD modelling only if a graphical relationship between perampanel exposure and change from baseline in CBCL score (participants aged >5 to <12 years) could be discerned. | Baseline up to Week 23 | |
| Secondary | Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Dominant Hand in Core Phase of This Study for All Participants Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanell | The Lafayette Grooved Pegboard Test (LGPT) measures visuomotor skills. This test is a manipulative dexterity test that consist of a metal matrix of 25 holes with randomly positioned slots. Participants require to insert 10 grooved pegs into the holes. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task is timed and the scores are the time taken for the participant to complete all 10 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds are recorded for the time. An increase in score (longer time) indicate worsening of visuomotor skills. Analysis for this outcome measure was planned to be performed via PK/PD modelling only if a graphical relationship between perampanel exposure and change from baseline in Total Time to Complete LGPT Score for Dominant Hand could be discerned. | Baseline up to Week 23 | |
| Secondary | Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Non-dominant Hand in Core Phase of This Study for All Participants Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel | The Lafayette Grooved Pegboard Test (LGPT) measures visuomotor skills. This test is a manipulative dexterity test that consist of a metal matrix of 25 holes with randomly positioned slots. Participants require to insert 10 grooved pegs into the holes. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task is timed and the scores are the time taken for the participant to complete all 10 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds are recorded for the time. An increase in score (longer time) indicate worsening of visuomotor skills. Analysis for this outcome measure was planned to be performed via PK/PD modelling only if a graphical relationship between perampanel exposure and change from baseline in Total Time to Complete LGPT Score for Non-dominant Hand could be discerned. | Baseline up to Week 23 | |
| Secondary | Percentage of Participants With Most Frequent Treatment Emergent Adverse Events (AEs) for Total Group of Participants That Were Considered Related to Perampanel- Core Phase of This Study | Baseline up to 23 weeks | ||
| Secondary | Change From Baseline in Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | The ABNAS assessment measured 5 aspects of cognitive function such as fatigue, memory, concentration, motor speed, and reading. The assessment was a measure of participant-perceived cognitive effects of AEDs. This instrument was aimed at assessing participant perceived drug-related cognitive impairment. Total score ranged from 0-72. Higher scores indicate a worsening of these cognitive functions. | Baseline, Week 23, Week 52 | |
| Secondary | Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 1.5 to 5 Years) as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | The CBCL for participants (age group 1.5 to 5 years) is a questionnaire to assess behavioral and emotional problems in children as reported by the primary caregiver for the following domains activities: emotionally reactive, anxious/depressed, withdrawn, somatic complaints, internalizing, attention problems, aggressive behavior, externalizing, sleep problems. CBCL total score for participants (age group 1.5 to 5 years) ranged from 0 to 200, was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior. | Baseline, Week 23, Week 52 | |
| Secondary | Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 6 to 18 Years) as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | The CBCL for participants (age group 6 to 18 years) is a questionnaire to assess behavioral and emotional problems in children as reported by the primary caregiver for the following domains activities: activity, social, school, total competence, anxious/depressed, withdrawn/depressed, somatic complaints, internalizing, rule-breaking behavior, aggressive behavior, externalizing, social problems, thought problems, attention problems. CBCL total score for participants (age group 6 to 18 years) ranged from 0 to 240, was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior. | Baseline, Week 23, Week 52 | |
| Secondary | Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores for 8 Years and Under as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | The LGPT test measured visuomotor skills. This test was a manipulative dexterity test that consisted of a metal matrix of 25 holes with randomly positioned slots. The participant was required to insert 10 grooved pegs into the holes. The task was completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task was timed and the scores were the time taken for the participant to complete all 10 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds were recorded for the time. An increase in score (longer time) indicated worsening of visuomotor skills. The time to complete test is presented as mean seconds plus/minus (+/-) SD. | Baseline, Week 23, Week 52 | |
| Secondary | Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores Over 8 Years as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | The LGPT test measured visuomotor skills. This test was a manipulative dexterity test that consisted of a metal matrix of 25 holes with randomly positioned slots. The participant was required to insert 25 grooved pegs into the holes. The task was completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task was timed and the scores were the time taken for the participant to complete all 25 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds were recorded for the time. An increase in score (longer time) indicated worsening of visuomotor skills. The time to complete test is presented as mean seconds +/- SD. | Baseline, Week 23, Week 52 | |
| Secondary | Change From Baseline in Height (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | Baseline, Week 23, Week 52 | ||
| Secondary | Change From Baseline in Weight (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | Baseline, Week 23, Week 52 | ||
| Secondary | Change From Baseline in Thyrotropin Value (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | Thyrotropin level was measured in milli-international units per liter (mIU/L). | Baseline, Week 23, Week 52 | |
| Secondary | Change From Baseline in Thyroxine, Free and Triiodothyronine, Free Values (Growth and Development Parameters) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | Baseline, Week 23, Week 52 | ||
| Secondary | Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Values (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study | Baseline, Week 23, Week 52 | ||
| Secondary | Percentage of Participants With Change From Baseline in Markedly Abnormal Encephalogram (EEG) Parameter Values During Awake and Sleep State for Total Group of Participant: Core Phase and Extension Phase A of This Study | Baseline up to 52 weeks | ||
| Secondary | Number of Encephalogram (EEG) Abnormalities During Awake and Sleep State for Total Group of Participant: Core Phase and Extension Phase A of This Study | Baseline up to 52 weeks | ||
| Secondary | Percentage of Participants With Any Treatment-emergent Reports of Suicidal Ideation and Behavior Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)- Core Phase and Extension Phase A of This Study | C-SSRS: interview-based instrument to systematically assess suicidal ideation (SI) and behavior, to assess whether participant experienced any of following: completed suicide, suicide attempt (response of "yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active SI with methods without intent to act or some intent to act, without or with specific plan and intent), any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior").Here, percentage of participants with >=1 positive behavior, participants with >=1 positive ideations; suicidality were reported.An assessment of SI and behavior with C-SSRS performed for participants >=6 years at time of consent. | Up to 52 weeks | |
| Secondary | Percentage of Participants With Shift From Baseline in Suicidal Ideation and Behaviors Assessed Using C-SSRS Scores to Extension Phase A (Week 52) of This Study | The C-SSRS: interview-based instrument to systematically assess suicidal ideation (SI) and suicidal behavior, to assess whether participant experienced any of the following: completed suicide, suicide attempt (response of "yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active SI with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). "w/" refers to "with", "W" refers to "Week" and "&" refers to "and". | Up to 52 weeks | |
| Secondary | Median Percent Change in Seizure Frequency Per 28 Days During the Treatment Phase Relative to the Pretreatment Phase (Baseline)- Core Phase and Extension Phase A of This Study | Seizure frequency was based on number of seizures per 28 days, calculated as number of seizures over entire time interval divided by number of days in interval and multiplied by 28. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with secondary generalization (SG). Data for this measure has been reported for 13 week time periods as per age groups. | Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52 | |
| Secondary | Percentage of Participants Based on 25% Responder Rate- Core Phase and Extension Phase A of This Study | A 25% responder was a participant who experienced a 25% or greater reduction in seizure frequency per 28 days from baseline. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this outcome measure has been reported for 13 week time periods as per age groups. | Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52 | |
| Secondary | Percentage of Participants Based on 50% Responder Rate- Core Phase and Extension Phase A of This Study | A 50% responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days from baseline. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this outcome measure has been reported for 13 week time periods as per age groups. | Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52 | |
| Secondary | Percentage of Participants Based on 75% Responder Rate- Core Phase and Extension Phase A of This Study | A 75% responder was a participant who experienced a 75% or greater reduction in seizure frequency per 28 days from baseline. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this outcome measure has been reported for 13 week time periods as per age groups. | Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52 | |
| Secondary | Percentage of Participants Who Were Seizure-free- Core Phase and Extension Phase A of This Study | Participants were considered seizure free if participants completed a 13-week time period and were seizure-free for that entire time period. Total POS: sum of all POS including simple partial seizures without motor signs, simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with SG. Data for this outcome measure has been reported for 13 week time periods as per age groups. | Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52 | |
| Secondary | Percentage of Participants With Clinical Global Impression of Change Scores (CGIC)- Core Phase and Extension Phase A of This Study | Assessment of disease severity utilized the CGIC scale at end of treatment to evaluate participant's change in disease status from baseline. The CGIC is a 7-point scale that measures a physician's global impression of a participant's clinical condition. Scale ranged from 1 to 7 with lower score indicated improvement (1=very much improved, 2=much improved, 3=minimally improved), higher score indicated worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicated no change. | Baseline, Week 23, Week 52 |