Clinical trial NCT02914314: Pharmacokinetic Study With an Oral Suspension of Perampanel as Adjunctive Therapy in Pediatric Subjects With Epilepsy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Keywords: epilepsy
refractory partial seizures
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-26
Enrollment: 26
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: 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
timeFrame: 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)
measure: Dose Normalized Maximum (Peak) Steady-state Concentration (Cmax,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants
timeFrame: 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)
measure: Dose Normalized Average Steady-state Drug Concentration (Css,Av) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants
timeFrame: 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)
measure: Dose Normalized Minimum Observed Steady State Plasma Concentration (Cmin,ss) of Perampanel During the Maintenance Period of the Core Phase for Non-EIAED Participants
timeFrame: 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)
measure: Dose Normalized AUCtau,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants
timeFrame: 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)
measure: Dose Normalized Cmax,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants
timeFrame: 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)
measure: Dose Normalized Css,Av of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants
timeFrame: 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)
measure: Dose Normalized Cmin,ss of Perampanel During the Maintenance Period of the Core Phase for EIAED Participants
timeFrame: 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:
measure: Core Phase and Extension Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameter: Erythrocytes
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Hematology Laboratory Parameter: Hemoglobin
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: 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
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameter: Bilirubin
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Creatinine, Direct Bilirubin, Urate
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Clinical Chemistry Laboratory Parameters: Albumin, Globulin, Protein
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Pulse Rate
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Respiratory Rate
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Vital Sign Parameter: Body Temperature
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Height
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Weight
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Head Circumference
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: 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
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in ECG Parameter: ECG Ventricular Rate
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH): Thyrotropin
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1)
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
measure: Core Phase and Extension Phase: Mean Change From Baseline in Free Thyroxine, and Free Triiodothyronine
timeFrame: Core Phase: Baseline, end of Core Phase treatment (up to Week 20); Extension Phase: Baseline (Core Phase), end of Extension Phase treatment (Week 52)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group, LL-ClinEdge- PPDS
state: Florida
city: Loxahatchee Groves
country: United States
facility: Axcess Medical Research
state: Florida
city: Orlando
country: United States
facility: Pediatric Neurology PA
state: Florida
city: Tampa
country: United States
facility: Pediatric Epilepsy And Neurology Specialists
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Children's Hospital at Saint Peter's University Hospital
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center, Children's Health Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Medical Center PPDS
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research, Ltd
state: Texas
city: Riga
country: Latvia
facility: Children's Clinical University Hospital
Study officials:
References: