Pharmacokinetic Study With an Oral Suspension of Perampanel as Adjunctive Therapy in Pediatric Subjects With Epilepsy

An Open-Label Study With an Extension Phase to Evaluate the Pharmacokinetics of Perampanel (E2007) Oral Suspension When Given as an Adjunctive Therapy in Subjects From 1 Month to Less Than 4 Years of Age With Epilepsy

The purpose of this study is to evaluate the pharmacokinetics (PK) of perampanel during the Maintenance Period of the Core Study following oral suspension administration given as an adjunctive therapy in pediatric participants from 1 month to less than 4 years of age with epilepsy.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: perampanel

Detailed Description

This is a multicenter, open-label study comprised of pretreatment, treatment (core study), and extension phases that is designed to evaluate the PK of an oral suspension of perampanel (maximum dose must not exceed 12 milligrams per day [mg /day] for participants taking non-enzyme-inducing antiepileptic drug [non-EIAED] or 16 mg/day for participants taking EIAED) when given as an adjunctive therapy in participants ranging from 1 month to less than 4 years of age with epilepsy. The Pretreatment Phase will last up to 2 weeks, during which participants will be assessed for their eligibility to participate in the study. The Treatment Phase will consist of 3 periods: Titration (12 [for participants taking non-EIAED] to 16 weeks [for participants taking EIAED]), Maintenance (4 weeks), and Follow-Up (4 weeks; only for those participants who complete the Maintenance Period but do not continue into the Extension Phase and those participants who discontinue study participation). Extension Phase: The Extension Phase will consist of 2 periods: Maintenance (32 weeks [for participants taking EIAED]; 36 weeks [for participants taking non-EIAED]) and Follow-Up (4 weeks).

The maximum total duration of treatment for each participant will be 52 weeks and the maximum total duration of the study for each participant will be 58 weeks (2 weeks Pretreatment+52 weeks of treatment+4 weeks Follow-up).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Latvia
  • Riga, Latvia, LV-1004
    • Children's Clinical University Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90095-1752
      • David Geffen School of Medicine at UCLA
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • NW FL Clinical Research Group, LL-ClinEdge- PPDS
    • Loxahatchee Groves, Florida, United States, 33470
      • Axcess Medical Research
    • Orlando, Florida, United States, 32819
      • Pediatric Neurology PA
    • Tampa, Florida, United States, 33609
      • Pediatric Epilepsy and Neurology Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Carle Foundation Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0284
      • University of Kentucky
  • Missouri
    • Kansas City, Missouri, United States, 64108-4619
      • Children's Mercy Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Children's Hospital at Saint Peter's University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center, Children's Health Center
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist Medical Center PPDS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Austin, Texas, United States, 78749
      • Child Neurology Consultants of Austin
    • San Antonio, Texas, United States, 78249
      • Road Runner Research, Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, from 1 month to less than 4 years of age (and of at least 36 weeks gestational age) at the time of consent
• Have a minimum weight of 4 kilograms (kg) (8.8 pounds [lb])
• Have a diagnosis of epilepsy with any type of seizure according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981). Diagnosis should have been established at least 2 weeks (≤6 months of age) or 4 weeks (>6 months of age) before Visit 1, by clinical history and an electroencephalogram (EEG) that is consistent with epilepsy; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (i.e., clinical history)
• Have had brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) before Visit 1 that ruled out a progressive cause of epilepsy
• Have had 1 or more seizure(s) before Visit 1
• Currently being treated with a stable dose (i.e., unchanged for at least 5 half-lives) of 1 to a maximum of 4 antiepileptic drugs (AEDs) (at least 6, but not more than 8, in the age group of 1 to less than 24 months, and up to 13 subjects in the age group of 2 to less than 4 years, will be taking 1 EIAEDs [that is, carbamazepine (CBZ), oxcarbazepine (OXC), phenytoin (PHT), or eslicarbazepine (ESL)] out of the maximum of 4 AEDs. The remaining participants cannot be taking any EIAEDs).
• Have been on their current concomitant AED(s) with a stable dose for at least 2 weeks or 5 half-lives, whichever is longer, before Visit 1
• Must have discontinued all restricted medications (example, medications known to be inducers of cytochrome P450 3A) at least 2 weeks or 5 half-lives (whichever is longer) before Visit 1
• If entering the Extension Phase, must have completed the last visit of the Maintenance Period of the Core Study

Exclusion Criteria:

• Have a history of status epilepticus that required hospitalization during the 3 months before Visit 1
• Have seizures due to treatable medical conditions, such as those arising due to metabolic disturbances, toxic exposure, or an active infection
• Have epilepsy secondary to progressive central nervous system (CNS) disease or any other progressive neurodegenerative disease, including tumors
• Have had epilepsy surgery within 1 year of Visit 1
• Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1
• Used intermittent rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period considered one-time rescue) 2 or more times in the 2 weeks before Visit 1
• Current use of felbamate, or any evidence of ongoing hepatic or bone marrow dysfunction associated with prior felbamate treatment. (Prior use of felbamate must be discontinued at least 8 weeks before Visit 1.)
• Current use of vigabatrin or any evidence of clinically significant vision abnormality associated with prior vigabatrin treatment. (Prior use of vigabatrin must be discontinued at least 2 weeks before Visit 1.)
• Are on ketogenic diet regimen that has not been stable for at least 4 weeks before Visit 1
• Concomitant use of other drugs known to influence the CNS, (other than AEDs for epilepsy), where the dose has not been stabilized for at least 5 half-lives or 2 weeks, whichever is longer, before Visit 1
• Have any concomitant illnesses/co-morbidities that could severely affect the participant's safety or study conduct
• Have evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or study conduct
• Have clinically significant laboratory abnormalities or any clinically acute or chronic disease
• Have 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)
• Have clinical evidence of significant active hematological disease; white blood cell (WBC) count ≤2500/ microliter (μL) (2.50 x 10^9/Liter [L]) or an absolute neutrophil count ≤1000/μL (1.00 x 10^9/L)
• Have conditions that may interfere with their participation in the study and/or with the PK of study drug
• 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
• Have recently (within 30 days before Visit 1) been exposed to perampanel in a clinical study or by prescription, and/or previous discontinuation from perampanel treatment due to adverse events related to perampanel
• Have a clinically significant ECG abnormality, including prolonged corrected QT interval (QTc) defined as >450 milliseconds (msec)
• Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Perampanel up to 12 or 16 mg/day; Pediatric participants, ranging from 1 month to less than 4 years of age, will receive perampanel oral suspension once a day in titration period starting at Week 0 at a dose of 0.50 mg per day (mg/day) titrated up to 4 mg/day (for participants taking non-EIAED) or up to 8 mg/day (for participants taking EIAED). Depending on participants clinical response, tolerability and investigator's decision, dose can be up titrated to 6 mg/day (for participants taking non-EIAED) and up titrated to 8 mg/day (for participants taking EIAED). Dose titration must not exceed 12 mg/day (non-EIAED) and 16 mg/day (EIAED). Participants will continue taking the perampanel oral suspension at dose level achieved at end of titration period through maintenance period of core study and maintenance period of extension phase (Up to Week 52).

Drug: perampanel; oral suspension.; Other Names: E2007

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Normalized Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is the area under the curve during a dosing interval (tau, 24 hours) at steady state calculated using population pharmacokinetic (PK) model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated liquid chromatography mass spectrometry (LC MS/MS) analytical method.	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Dose normalized Cmax,ss was calculated as Cmax,ss/maintenance dose, where Cmax,ss is the maximum (peak) steady-state concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as the ratio of area under the curve (AUC)/tau, (tau = 24 hours for perampanel) using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants	Dose normalized Cmin,ss was calculated as Cmin,ss/maintenance dose, where Cmin,ss is the minimum observed steady state plasma concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 99 and 113 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 99 and 113: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 99 and 113: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Dose normalized AUCtau,ss was calculated as AUCtau,ss/maintenance dose, where AUCtau,ss is the area under the curve during a dosing interval (tau, 24 hours) at steady state calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Dose normalized Cmax,ss was calculated as Cmax,ss/maintenance dose, where Cmax,ss is the maximum (peak) steady-state concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Dose normalized Css,Av was calculated as Css,Av/maintenance dose. Css,Av of perampanel was calculated as the ratio of area under the curve (AUC)/tau, (tau = 24 hours for perampanel) using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)
Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants	Dose normalized Cmin,ss was calculated as Cmin,ss/maintenance dose, where Cmin,ss is the minimum observed steady state plasma concentration calculated using population PK model. PK sparse sampling was performed. One sample was collected at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 1, Cohort 2, Cohort 3) and two samples were collected, one at pre-dose and other at anytime between 1 to 5 hours post-dose on Days 127 and 141 (Cohort 4). Plasma concentrations of perampanel were measured and concentration data were summarized. Plasma concentrations of perampanel were quantified using a validated LC MS/MS analytical method.	Maintenance Period of the Core Phase- Days 127 and 141: 1-5 hours post-dose (Cohort 1, Cohort 2, Cohort 3); Days 127 and 141: Pre-dose, 1-5 hours post-dose (Cohort 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase and Extension Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAE was an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline); or re-emerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment; or worsened in severity during treatment relative to the pretreatment state, when AE was continuous. SAE was any untoward medical occurrence that at any dose: Resulted in death; was life-threatening (meaning participant was at an immediate risk of death from AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect (in child of a participant who was exposed to the study drug).	Core Phase: From the first dose of study drug up to 4 weeks of follow up after the last dose in Core Phase (up to Week 24); Extension Phase: From end of Core Phase treatment up to 4 weeks of follow up after the last dose in Extension Phase (up to Week 56)
Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets	Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, and platelets were expressed as 10^9 cells per liter (/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameter: Erythrocytes	Erythrocytes was expressed as 10^12 cells/L. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameter: Hemoglobin	Hemoglobin was expressed as grams per liter (g/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Lactate Dehydrogenase	Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase were expressed as units per liter (U/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin	Bilirubin was expressed as micromoles per liter (mcmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen	Calcium, chloride, cholesterol, glucose, phosphate, potassium, sodium, triglycerides, urea nitrogen were expressed as millimoles per liter (mmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate	Creatinine, direct bilirubin, urate were expressed as micromoles per liter (mcmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein	Albumin, globulin, protein were expressed as g/L. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	SBP and DBP were measured after the participant sitting or supine, for 5 minutes. SBP and DBP were expressed as millimeter of mercury (mmHg). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate	Pulse rate measured after the participant sitting or supine, for 5 minutes and was expressed in beats per minute (beats/min). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate	Respiratory rate was the number of breaths taken per minute, measured at rest. Respiratory rate was expressed as breaths per minute (breaths/min). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature	Body temperature was expressed as degree centigrade. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Height	Height was expressed as centimeters. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Weight	Weight was expressed as kilograms. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference	Head circumference was expressed as centimeters. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core and Extension Phase: Mean Change From Baseline in ECG Parameters: Single Beat Heart Rate-corrected QT Interval (QTcB), QT Interval Corrected According to the Formula of Fridericia (QTcF), PR and QT Intervals, QRS Duration, and Aggregate RR Interval	QTc: time from beginning of QRS complex to end of T wave, corrected for heart rate. QT interval: time from ECG Q wave to end of T wave corresponding to electrical systole. QRS interval: time from ECG Q wave to end of S wave, corresponding to ventricle depolarization. PR interval: time between beginning of P wave and start of QRS interval, corresponding to end of atrial depolarization and onset of ventricular depolarization. RR interval: time elapsed between two successive R waves of QRS signal. Single beat QTcB, QTcF, PR and QT Interval, QRS duration and aggregate RR interval were expressed as millisecond (msec). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in ECG Parameter: ECG Ventricular Rate	Ventricular rate is determined by dividing 60 by the mean RR interval of the ECG in seconds (mean time between QRS complexes) to get beats per minute. ECG ventricular rate was expressed as beats/min. Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin	Thyrotropin was expressed as milli-international units per liter (mIU/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)	IGF-1 was expressed as millimoles per liter*10^-6 (mmol/L*10^-6). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameter was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Core Phase and Extension Phase: Mean Change From Baseline in Free Thyroxine, and Free Triiodothyronine	Free thyroxine, and free triiodothyronine were expressed as picomoles per liter (pmol/L). Change from baseline was calculated as post-baseline absolute value minus baseline value. Baseline values of Core Phase was used to calculate the change from baseline data for Extension Phase. Mean change from baseline data at end of Core Phase and at end of Extension Phase treatment for specified parameters was reported.	Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2017
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): April 25, 2023

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: September 22, 2016
• First Posted (Estimated): September 26, 2016

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: epilepsy; refractory partial seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: E2007-G000-238

Drug and device information, study documents

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