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

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ClinicalTrials.gov Identifier: NCT02914314
Recruitment Status : Recruiting
First Posted : September 26, 2016
Last Update Posted : June 1, 2020
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Tracking Information
First Submitted Date  ICMJE May 26, 2016
First Posted Date  ICMJE September 26, 2016
Last Update Posted Date June 1, 2020
Actual Study Start Date  ICMJE February 20, 2017
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2020)
  • Average steady-state drug concentration (Css,av) of perampanel during the Maintenance Period of the Core Study (Non-EIAED) [ Time Frame: 113 Days ]
    Blood samples (1.0 mL) will be collected from all non-EIAED participants for the determination of perampanel concentrations. The average steady-state concentration is the average concentration of perampanel in plasma at the time that a steady state has been achieved, and rates of drug administration and drug elimination are equal.
  • Steady-state peak concentration (Cmax,ss) of perampanel during the Maintenance Period of the Core Study (Non-EIAED) [ Time Frame: 113 Days ]
    Blood samples (1.0 mL) will be collected from all non-EIAED participants for the determination of perampanel concentrations. The peak steady-state concentration is the maximum concentration of perampanel in plasma at the time that a steady state has been achieved, and rates of drug administration and drug elimination are equal.
  • Area under the concentration versus time curve at steady state (AUCss) of perampanel during the Maintenance Period of the Core Study (Non-EIAED) [ Time Frame: 113 Days ]
    Blood samples (1.0 mL) will be collected from all non-EIAED participants for the determination of perampanel concentrations. AUC represents the total drug exposure over a defined period of time.
  • Average steady-state drug concentration (Css,av) of perampanel during the Maintenance Period of the Core Study (EIAED) [ Time Frame: 141 Days ]
    Blood samples (1.0 mL) will be collected from all EIAED participants for the determination of perampanel concentrations. The average steady-state concentration is the average concentration of perampanel in plasma at the time that a steady state has been achieved, and rates of drug administration and drug elimination are equal.
  • Steady-state peak concentration (Cmax,ss) of perampanel during the Maintenance Period of the Core Study (EIAED) [ Time Frame: 141 Days ]
    Blood samples (1.0 mL) will be collected from all EIAED participants for the determination of perampanel concentrations. The peak steady-state concentration is the maximum concentration of perampanel in plasma at the time that a steady state has been achieved, and rates of drug administration and drug elimination are equal.
  • Area under the concentration versus time curve at steady state (AUCss) of perampanel during the Maintenance Period of the Core Study (EIAED) [ Time Frame: 141 Days ]
    Blood samples (1.0 mL) will be collected from all EIAED participants for the determination of perampanel concentrations. AUC represents the total drug exposure over a defined period of time.
Original Primary Outcome Measures  ICMJE
 (submitted: September 22, 2016)
  • Absorption rate of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days (non-enzyme-inducing [non-EIAED] participants) ]
  • Apparent clearance of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days (non-enzyme-inducing [non-EIAED] participants) ]
  • Apparent central and peripheral volumes of distribution of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days (non-enzyme-inducing [non-EIAED] participants) ]
  • Average steady-state drug concentration (Css,av) of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days (non-enzyme-inducing [non-EIAED] participants) ]
  • Steady-state peak concentration (Cmax,ss) of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days (non-enzyme-inducing [non-EIAED] participants) ]
  • Area under the concentration versus time curve at steady state (AUCss) of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days (non-enzyme-inducing [non-EIAED] participants) ]
  • Absorption rate of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days (EIAED participants) ]
  • Apparent clearance of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days (EIAED participants) ]
  • Apparent central and peripheral volumes of distribution of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days (EIAED participants) ]
  • Average steady-state drug concentration (Css,av) of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days (EIAED participants) ]
  • Steady-state peak concentration (Cmax,ss) of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days (EIAED participants) ]
  • Area under the concentration versus time curve at steady state (AUCss) of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days (EIAED participants) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2020)
  • Number of participants with any treatment-emergent adverse events (TEAEs) and any TE serious adverse event (SAE) [ Time Frame: Up to Week 56 ]
    A TEAE is defined as an AE that emerges during treatment, having been absent at pretreatment (Baseline); or re-emerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment; or worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.
  • Mean change from Baseline in the indicated clinical laboratory parameters [ Time Frame: Up to Week 52 ]
    Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value of the indicated laboratory parameters.
  • Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Up to Week 52 ]
    Blood pressure will be measured after the participant has been sitting or supine, for 5 minutes. All BP measurements should be performed on the same arm, preferably by the same person. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in pulse rate [ Time Frame: Up to Week 52 ]
    Pulse rate will be expressed in beats per minute. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in respiratory rate [ Time Frame: Up to Week 52 ]
    Respiratory rate is the number of breaths taken in a specified time, usually per minute, measured at rest. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in body temperature [ Time Frame: Up to Week 52 ]
    Body temperature is measured using a thermometer and will be expressed in centigrade. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in 12-lead electrocardiogram (ECG) findings [ Time Frame: Up to Week 52 ]
    If the participant has a normal ECG Baseline reading, but during any visit thereafter there is any clinically significant ECG abnormality (as determined by the investigator), 3 consecutive ECGs separated by 5 to 10 minutes will be performed at that visit to confirm the abnormality. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in height [ Time Frame: Up to Week 52 ]
    Two measurements of height/length will be taken. Each measurement will be recorded as a separate entry. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in weight [ Time Frame: Up to Week 52 ]
    Weight is measured in kilograms (kg). Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in head circumference [ Time Frame: Up to Week 52 ]
    Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) [ Time Frame: Up to Week 52 ]
    Blood samples (1.0 mL) will be collected from all participants for the determination of TSH, fT3, and fT4. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
  • Mean change from Baseline in insulin-like growth factor 1 (IGF-1) [ Time Frame: Up to Week 52 ]
    Blood samples (1.0 mL) will be collected from all participants for the determination of IGF-1. Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2016)
  • Number of participants with any treatment-emergent adverse events (TEAEs) and any TE serious adverse event (SAE) [ Time Frame: Up to Week 56 ]
  • Mean change from Baseline in the indicated clinical laboratory parameters [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in pulse [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in respiratory rate [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in body temperature [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in 12-lead electrocardiogram (ECG) findings [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in height [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in weight [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in head circumference [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) [ Time Frame: up to Week 56 ]
  • Mean change from Baseline in insulin-like growth factor 1 (IGF-1) [ Time Frame: up to Week 56 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Study With an Oral Suspension of Perampanel as Adjunctive Therapy in Pediatric Subjects With Epilepsy
Official Title  ICMJE 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
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE Drug: perampanel
oral suspension.
Other Name: E2007
Study Arms  ICMJE 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).
Intervention: Drug: perampanel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2020)
50
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2016)
16
Estimated Study Completion Date  ICMJE September 30, 2020
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 4 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eisai Medical Information 1-888-274-2378 esi_medinfo@eisai.com
Listed Location Countries  ICMJE Czechia,   Latvia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02914314
Other Study ID Numbers  ICMJE E2007-G000-238
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc.
Study Sponsor  ICMJE Eisai Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Eisai Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP