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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 : October 18, 2017
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The purpose of this study is to evaluate the pharmacokinetics (PK) of an oral suspension of perampanel given as an adjunctive therapy and to generate preliminary safety and efficacy data in pediatric participants, ranging from 1 month to less than 24 months of age, with epilepsy.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: perampanel Phase 2

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 (target dose of 12 milligrams per day [mg /day] for non-enzyme-inducing antiepileptic drug [non-EIAED] or 16 mg/day for EIAED) when given as an adjunctive therapy in participants ranging from 1 month to less than 24 months (<2 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 to 16 weeks), 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). The Extension Phase will consist of 2 periods: Maintenance (32 to 36 weeks) 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 (52 weeks of treatment + 2 weeks of pretreatment + 4 weeks of follow-up).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 24 Months (<2 Years) of Age With Epilepsy
Actual Study Start Date : February 20, 2017
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy
Drug Information available for: Perampanel

Arm Intervention/treatment
Experimental: Perampanel 12 or 16 mg/day
Pediatric participants, ranging from 1 month to less than 24 months of age, will receive a target dose of perampanel 12 mg/day (non-enzyme-inducing antiepileptic drug [non-EIAED] participants) or 16 mg/day (EIAED participants) administered as an oral suspension once a day for up to 24 weeks.
Drug: perampanel
oral suspension
Other Name: E2007




Primary Outcome Measures :
  1. Absorption rate of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days ]
    Blood samples (1.0 milliliter [mL]) will be collected from all non-enzyme-inducing (non-EIAED) participants for the determination of perampanel concentrations. Absorption rate is defined as the fractional rate of perampanel absorption from the site of administration into the systemic circulation.

  2. Apparent clearance of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days ]
    Blood samples (1.0 mL) will be collected from all non-EIAED participants for the determination of perampanel concentrations. Apparent clearance is defined as the rate of perampanel elimination divided by plasma concentration, giving a volume of plasma from which drug is completely removed per unit of time.

  3. Apparent central and peripheral volumes of distribution of perampanel during the Maintenance Period of the Core Study [ Time Frame: 113 Days ]
    Blood samples (1.0 mL) will be collected from all non-EIAED participants for the determination of perampanel concentrations. Volume of distribution is defined as the fluid volume that would be required to contain the amount of perampanel present in the body at the same concentration as in the plasma.

  4. Average steady-state drug concentration (Css,av) of perampanel during the Maintenance Period of the Core Study [ 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.

  5. Steady-state peak concentration (Cmax,ss) of perampanel during the Maintenance Period of the Core Study [ 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.

  6. 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 ]
    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.

  7. Absorption rate of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days ]
    Blood samples (1.0 mL) will be collected from all enzyme-inducing (EIAED) participants for the determination of perampanel concentrations. Absorption rate is defined as the fractional rate of perampanel absorption from the site of administration into the systemic circulation.

  8. Apparent clearance of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days ]
    Blood samples (1.0 mL) will be collected from all EIAED participants for the determination of perampanel concentrations. Apparent clearance is defined as the rate of perampanel elimination divided by plasma concentration, giving a volume of plasma from which drug is completely removed per unit of time.

  9. Apparent central and peripheral volumes of distribution of perampanel during the Maintenance Period of the Core Study [ Time Frame: 141 Days ]
    Blood samples (1.0 mL) will be collected from all EIAED participants for the determination of perampanel concentrations. Volume of distribution is defined as the fluid volume that would be required to contain the amount of perampanel present in the body at the same concentration as in the plasma.

  10. Average steady-state drug concentration (Css,av) of perampanel during the Maintenance Period of the Core Study [ 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.

  11. Steady-state peak concentration (Cmax,ss) of perampanel during the Maintenance Period of the Core Study [ 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.

  12. 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 ]
    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.


Secondary Outcome Measures :
  1. 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.

  2. Mean change from Baseline in the indicated clinical laboratory parameters [ Time Frame: up to Week 56 ]
    Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value of the indicated laboratory parameters.

  3. Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: up to Week 56 ]
    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.

  4. Mean change from Baseline in pulse rate [ Time Frame: up to Week 56 ]
    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.

  5. Mean change from Baseline in respiratory rate [ Time Frame: up to Week 56 ]
    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.

  6. Mean change from Baseline in body temperature [ Time Frame: up to Week 56 ]
    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.

  7. Mean change from Baseline in 12-lead electrocardiogram (ECG) findings [ Time Frame: up to Week 56 ]
    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.

  8. Mean change from Baseline in height [ Time Frame: up to Week 56 ]
    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.

  9. Mean change from Baseline in weight [ Time Frame: up to Week 56 ]
    Weight is measured in kilograms (kg). Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.

  10. Mean change from Baseline in head circumference [ Time Frame: up to Week 56 ]
    Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.

  11. Mean change from Baseline in thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) [ Time Frame: up to Week 56 ]
    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.

  12. Mean change from Baseline in insulin-like growth factor 1 (IGF-1) [ Time Frame: up to Week 56 ]
    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.



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Ages Eligible for Study:   1 Month to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, from 1 to less than 24 months (<2 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 3 antiepileptic drugs (AEDs) (at least 6, but not more than 8, participants will be taking 1 enzyme-inducing AED [EIAEDs] out of the maximum of 3 AEDs allowed. The remaining participants cannot be taking any EIAEDs).
  • Have been on their current concomitant AED regime with a stable dose for at least 2 weeks (≤6 months of age) or 4 weeks (>6 months of age) before Visit 1
  • Must have discontinued all restricted medications 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
  • Prior use of felbamate
  • Prior use of vigabatrin
  • Are on ketogenic diet regimen that has not been stable for at least 4 weeks before Visit 1
  • Have used other drugs known to influence the CNS, where the dose has not been stabilized for at least 2 weeks (≤6 months of age) or 4 weeks (>6 months of age) 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 previously participated in a clinical trial involving 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02914314


Contacts
Contact: Eisai Medical Information 1-888-274-2378 esi_medinfo@eisai.com

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
United States, Florida
NW FL Clinical Research Group, LLC Recruiting
Gulf Breeze, Florida, United States, 32561
Pediatric Neurologists of Palm Beach Recruiting
Loxahatchee Groves, Florida, United States, 33470
Pediatric Neurology PA Recruiting
Orlando, Florida, United States, 32819
Pediatric Epilepsy and Neurology Specialists Recruiting
Tampa, Florida, United States, 33609
United States, Illinois
Carle Foundation Hospital Recruiting
Urbana, Illinois, United States, 61801
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536-0284
United States, Massachusetts
Boston Children's Hospital Withdrawn
Boston, Massachusetts, United States, 02115
United States, Missouri
Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108-4619
United States, North Carolina
Wake Forest Baptist Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
United States, Texas
Child Neurology Consultants of Austin Recruiting
Austin, Texas, United States, 78731
Road Runner Research Ltd Recruiting
San Antonio, Texas, United States, 78258
United States, Utah
University of Utah Withdrawn
Salt Lake City, Utah, United States, 84113
Czechia
Fakultni nemocnice Brno Withdrawn
Brno, Czechia
Fakultni nemocnice Ostrava Withdrawn
Ostrava, Czechia
Fakultni nemocnice v Motole Withdrawn
Prague, Czechia
Latvia
Childrens University Hospital Recruiting
Riga, Latvia
Sponsors and Collaborators
Eisai Inc.

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02914314     History of Changes
Other Study ID Numbers: E2007-G000-238
First Posted: September 26, 2016    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:
epilepsy
refractory partial seizures

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases