Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
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) |
|
| Primary |
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) |
|
| Primary |
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) |
|
| Primary |
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) |
|
| Primary |
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) |
|
| Primary |
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) |
|
| Primary |
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) |
|
| Primary |
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 |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
