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

NCT ID: NCT02914314

Last Updated: 2024-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-20
• Study Completion Date: 2023-04-25

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.

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).

Conditions

Epilepsy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

perampanel

Intervention Type: DRUG

oral suspension.

Interventions

perampanel

oral suspension.

Intervention Type: DRUG

Other Intervention Names

E2007

Eligibility Criteria

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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

NW FL Clinical Research Group, LL-ClinEdge- PPDS

Gulf Breeze, Florida, United States

Axcess Medical Research

Loxahatchee Groves, Florida, United States

Pediatric Neurology PA

Orlando, Florida, United States

Pediatric Epilepsy And Neurology Specialists

Tampa, Florida, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Augusta University

Augusta, Georgia, United States

Carle Foundation Hospital

Urbana, Illinois, United States

University of Kentucky

Lexington, Kentucky, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Children's Hospital at Saint Peter's University Hospital

New Brunswick, New Jersey, United States

Duke University Medical Center, Children's Health Center

Durham, North Carolina, United States

Atrium Health Wake Forest Baptist Medical Center PPDS

Winston-Salem, North Carolina, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Child Neurology Consultants of Austin

Austin, Texas, United States

Road Runner Research, Ltd

San Antonio, Texas, United States

Children's Clinical University Hospital

Riga, , Latvia

Countries

United States; Latvia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

E2007-G000-238

Identifier Type: -

Identifier Source: org_study_id