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

NCT02914314 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: E2007-G000-238
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 18

Brief Summary

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.

Conditions

Epilepsy

Keywords

epilepsy; refractory partial seizures

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (21)

• Core Phase and Extension Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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

  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

  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

  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

  Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)

Study Arms (1)

Perampanel up to 12 or 16 mg/day

EXPERIMENTAL

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

Interventions

perampanel DRUG

oral suspension.

Also known as: E2007

Perampanel up to 12 or 16 mg/day

Eligibility Criteria

• Age: 1 Month - 4 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (18)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095-1752, United States

Location

NW FL Clinical Research Group, LL-ClinEdge- PPDS

Gulf Breeze, Florida, 32561, United States

Location

Axcess Medical Research

Loxahatchee Groves, Florida, 33470, United States

Location

Pediatric Neurology PA

Orlando, Florida, 32819, United States

Location

Pediatric Epilepsy And Neurology Specialists

Tampa, Florida, 33609, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0284, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108-4619, United States

Location

Children's Hospital at Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Duke University Medical Center, Children's Health Center

Durham, North Carolina, 27710, United States

Location

Atrium Health Wake Forest Baptist Medical Center PPDS

Winston-Salem, North Carolina, 27157, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Child Neurology Consultants of Austin

Austin, Texas, 78749, United States

Location

Road Runner Research, Ltd

San Antonio, Texas, 78249, United States

Location

Children's Clinical University Hospital

Riga, LV-1004, Latvia

Location

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

perampanel

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: September 26, 2016
• Study Start: February 20, 2017
• Primary Completion: August 23, 2022
• Study Completion: April 25, 2023
• Last Updated: March 15, 2024
• Results First Posted: September 15, 2023

Record last verified: 2023-05

Locations

LA (1); US (17)