Pharmacokinetics, Efficacy, and Safety of Perampanel Oral Suspension on Seizure Frequency in Pediatric Subjects Maintained on One to Three Stable Antiepileptic Drugs

NCT01527006 | Completed Phase 2 Results

• 1 other identifier: E2007-G000-232
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 23

Brief Summary

This study is designed to evaluate the pharmacokinetics, efficacy, and safety of perampanel oral suspension on seizure frequency in pediatric participants maintained on one to three stable antiepileptic drugs

Conditions

Central Nervous System

Outcome Measures

Primary Outcomes (2)

• Apparent Clearance (CL/F) of Perampanel [Core Study]

  CL/F was defined as the volume of plasma cleared of the drug per unit time. Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. The CL/F values were calculated for each visit and averaged to derive the total CL/F value per arm. Data was analyzed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/-standard deviation.

  From Day 8 up to Day 78

• Steady-state Average Concentration (C av,ss) of Perampanel [Core Study]

  C av,ss was calculated as 'Dose (mg)/Dosing Interval (24 h)/(CL/F \[L/h\]) x 1000'. C av,ss during a dosing interval was dose-normalized to 0.12 mg/kg in participants aged ≥ 2 to less than 12 years (intended to correspond to 8 mg/70 kg in adults/adolescents). Blood samples were collected at day 8, Day 36, Day 64 , and Day 78. C av,ss values were calculated for each visit and averaged to derive the total C av,ss value per arm. Data was analysed for 2 categories: CYP3A4/5 inducers (carbamazepine, oxcarbazepine and phenytoin) and non-inducers. Data is presented as mean Liter per hour +/- standard deviation.

  From Day 8 up to Day 78

Secondary Outcomes (13)

• Percent Change From Baseline in Seizure Frequency Per 28 Days in Treatment Phase [Core Study]

  Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 0 to Week 15

• 50% Responder Rate During the Maintenance Period-LOCF [Core Study]

  Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 9 to 11

• Seizure-free Rate During the Maintenance Period [Core Study]

  Week 9 to Week 11

• The Clinical Global Impression of Change at the End of Treatment (EOT) [Core Study]

  Week 0 (Baseline), Week 11 or EOT

• Number of Participants With Treatment Emergent Non-Serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel

  For each participant, from the first treatment dose till 30 days after the last dose or up to Week 15 for Core Study and Week 56 for the Extension Phase

Other Outcomes (6)

• The Effect of Demographics on Population PK Parameters: AUC

  11 weeks

• The Effect of Demographics on Population PK Parameters: Cmax

  11 weeks

• The Effect of Demographics on Population PK Parameters: Tmax

  11 weeks

Study Arms (1)

perampanel

EXPERIMENTAL

Age Cohort 1 ( greater than or equal to 7 to less than 12 years of age at time of consent/assent) and age Cohort 2 ( greater than or equal to 2 to less than 7 years of age).

Drug: perampanel

Interventions

perampanel DRUG

During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.

perampanel

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Have a minimum weight of 10 kg (22 lb)
• Have had brain imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) prior to Visit 1 that ruled out a progressive cause of epilepsy
• 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 6 months prior to 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 one or more seizure(s) during the 4 weeks prior to Visit 1
• Are currently being treated with stable doses of one to a maximum of three AEDs for at least 4 weeks prior to Visit 1 and throughout the study duration (Only one perampanel inducing AED \[i.e. carbamazepine, oxcarbazepine, phenytoin\] out of the maximum of 3 AEDs is allowed in at least one third of the participants in each age cohort and not to exceed one half of the population of each age cohort. The remaining participants should not be taking any inducer)
• Have been on their current concomitant AED regimen for 2 months or more with a stable dose for at least 4 weeks prior to Visit 1
• Must have discontinued all restricted medications at least 2 weeks or five half-lives (whichever is longer) prior to Visit 1
• Females aged at least 8 years or of child-bearing potential must have a negative serum beta-hCG at Visit 1 and a negative urine pregnancy test prior to titration at Visit 2. Female participants of childbearing potential must agree for the duration of the study and for a period of at least 60 days following administration of the last dose of study drug to be abstinent or commit to the consistent and correct use of a medically acceptable method of birth control (e.g., a double-barrier method \[condom + spermicide, condom + diaphragm with spermicide\])

You may not qualify if:

• Have a history of status epilepticus that required hospitalization during the 6 months prior to Visit 1
• Have current or a history of pseudo-seizures (psychogenic non-epileptic seizures \[PNES\]) from birth or within approximately 5 years prior to 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 cerebral disease or any other progressive neurodegenerative disease
• Have had epilepsy surgery within 1 year prior to Visit 1
• Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1; however, those who have previously documented failed epilepsy surgery will be allowed
• Use of intermittent rescue benzodiazepines (i.e. 1-2 doses over a 24-hour period considered one-time rescue) two or more times in a 30-day period prior to Visit 1
• If felbamate is used as a concomitant AED, participants must be on felbamate for at least 2 years, with a stable dose for 8 weeks prior to Visit 1. They must not have a history of white blood cell (WBC) count below 2500/L (2.50 x 10\^9/L), platelets below 100,000, liver function tests (LFTs) above 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate. If participants received felbamate in the past, it must have been discontinued 8 weeks prior to Visit 1
• Have concomitant use of vigabatrin: participants who took vigabatrin in the past must be off vigabatrin for approximately 5 months prior to Visit 1 and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in the visual perimetry test
• If ketogenic diet is used, participants must be on a stable regimen for at least 4 weeks prior to Visit 1
• Have previously participated in a clinical trial involving perampanel

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (23)

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Gulf Breeze, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Augusta, Georgia, United States

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Indianapolis, Indiana, United States

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Lexington, Kentucky, United States

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Shreveport, Louisiana, United States

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Chesterfield, Missouri, United States

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Columbia, Missouri, United States

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Gibbsboro, New Jersey, United States

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Buffalo, New York, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Memphis, Tennessee, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Richmond, Virginia, United States

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Related Publications (1)

• Renfroe JB, Mintz M, Davis R, Ferreira J, Dispoto S, Ferry J, Umetsu Y, Rege B, Majid O, Hussein Z, Laurenza A. Adjunctive Perampanel Oral Suspension in Pediatric Patients From >/=2 to <12 Years of Age With Epilepsy: Pharmacokinetics, Safety, Tolerability, and Efficacy. J Child Neurol. 2019 Apr;34(5):284-294. doi: 10.1177/0883073819827407. Epub 2019 Feb 10.

  PMID: 30739576 DERIVED

MeSH Terms

Interventions

perampanel

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Michelle Gee

  Eisai Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• 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: November 10, 2011
• First Posted: February 6, 2012
• Study Start: January 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: April 1, 2015
• Last Updated: July 12, 2016
• Results First Posted: August 28, 2015

Record last verified: 2016-06

Locations

US (23)