Clinical trial NCT01527006: Pharmacokinetics, Efficacy, and Safety of Perampanel Oral Suspension on Seizure Frequency in Pediatric Subjects Maintained on One to Three Stable Antiepileptic Drugs
Official title: An Open-label Pilot Study With an Extension Phase to Evaluate the Pharmacokinetics, and to Generate Preliminary Safety, Tolerability, and Efficacy of Perampanel (E2007) Oral Suspension When Given as an Adjunctive Therapy in Pediatric Subjects From 2 to Less Than 12 Years of Age With Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Central Nervous System
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2012-02-06
Enrollment: 63
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: This is a multicenter, multiple ascending dose, open-label study (Core Study) with an Extension Phase. The Core Study consisted of 2 phases, the Pretreatment Phase and the Treatment Phase. The Pretreatment Phase lasted up to 2 weeks in duration, during which participants were assessed for their eligibility to participate in the study. The Treatment Phase consisted of 3 periods: Titration (7 weeks), Maintenance (4 weeks), and Follow-up (4 weeks; only for those participants not rolling over into the Extension Phase after completing the Treatment Phase and for those participants who discontinued from the study). All subjects who completed all scheduled visits up to and including the final visit of the Treatment Phase (Core Study) were eligible to participate in the Extension Phase of the study. The Extension Phase consisted of 2 periods: Maintenance (41 weeks) and Follow-up (4 weeks).

Eligibility criteria: Inclusion:

1. Have a minimum weight of 10 kg (22 lb)
2. Have had brain imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) prior to Visit 1 that ruled out a progressive cause of epilepsy
3. 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)
4. Have had one or more seizure(s) during the 4 weeks prior to Visit 1
5. 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)
6. 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
7. Must have discontinued all restricted medications at least 2 weeks or five half-lives (whichever is longer) prior to Visit 1
8. 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 \[condom + spermicide, condom + diaphragm with spermicide\])

Exclusion:

1. Have a history of status epilepticus that required hospitalization during the 6 months prior to Visit 1
2. Have current or a history of pseudo-seizures (psychogenic non-epileptic seizures \[PNES\]) from birth or within approximately 5 years prior to Visit 1
3. Have seizures due to treatable medical conditions, such as those arising due to metabolic disturbances, toxic exposure, or an active infection
4. Have epilepsy secondary to progressive cerebral disease or any other progressive neurodegenerative disease
5. Have had epilepsy surgery within 1 year prior to Visit 1
6. 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
7. 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
8. 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
9. 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
10. If ketogenic diet is used, participants must be on a stable regimen for at least 4 weeks prior to Visit 1
11. Have previously participated in a clinical trial involving perampanel

Primary outcomes:
measure: Apparent Clearance (CL/F) of Perampanel [Core Study]
timeFrame: From Day 8 up to Day 78
measure: Steady-state Average Concentration (C av,ss) of Perampanel [Core Study]
timeFrame: From Day 8 up to Day 78
Secondary outcomes:
measure: Percent Change From Baseline in Seizure Frequency Per 28 Days in Treatment Phase [Core Study]
timeFrame: Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 0 to Week 15
measure: 50% Responder Rate During the Maintenance Period-LOCF [Core Study]
timeFrame: Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Week 9 to 11
measure: Seizure-free Rate During the Maintenance Period [Core Study]
timeFrame: Week 9 to Week 11
measure: The Clinical Global Impression of Change at the End of Treatment (EOT) [Core Study]
timeFrame: Week 0 (Baseline), Week 11 or EOT
measure: 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
timeFrame: 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
measure: Palatability Questionnaire Assessment - How Does This Medicine Taste [Core Study]
timeFrame: Week 5 or at the time of early discontinuation
measure: Palatability Questionnaire Assessment - How Does This Medicine Smell [Core Study]
timeFrame: Week 5 or at the time of early discontinuation
measure: Palatability Questionnaire Assessment - Based on Its Taste, Smell, and How it Felt in the Mouth, How Easy or Difficult Was it for You / Your Child to Take This Medicine Every Day [Core Study]
timeFrame: Week 5 or at the time of early discontinuation
measure: Palatability Questionnaire Assessment - Would You/Your Child Have Preferred This Medicine to Have Been Flavored, e.g. Fruity [Core Study]
timeFrame: Week 5 or at the time of early discontinuation
measure: Percentage Change From Baseline in Seizure Frequency Per 28 Days During the Overall Treatment Duration by 13-week Intervals [Extension Phase]
timeFrame: Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52
measure: 50 % Responder Rate During the Overall Treatment Duration by 13-week Intervals [Extension Phase]
timeFrame: Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52
measure: Seizure-free Rate During the Overall Treatment Duration [Extension Phase]
timeFrame: Baseline [2 weeks Pretreatment Phase (Visit 1) plus 4 weeks Prior to Pretreatment Phase], Weeks 1-13, Weeks 14-26, Weeks 27-39, and Weeks 40-52
measure: The Clinical Global Impression of Change During the Overall Treatment Duration by Visit and at EOT [Extension Phase]
timeFrame: Week 0 (Baseline), Week 11, Week 28, Week 52 or EOT
Other outcomes:
measure: The Effect of Demographics on Population PK Parameters: AUC
timeFrame: 11 weeks
measure: The Effect of Demographics on Population PK Parameters: Cmax
timeFrame: 11 weeks
measure: The Effect of Demographics on Population PK Parameters: Tmax
timeFrame: 11 weeks
measure: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: AUC
timeFrame: 11 weeks
measure: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Cmax
timeFrame: 11 weeks
measure: The Effect of the Most Common Concomitant AEDs on Population PK Parameters: Tmax
timeFrame: 11 weeks
Locations:
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Gulf Breeze
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Shreveport
country: United States
state: Louisiana
city: Chesterfield
country: United States
state: Missouri
city: Columbia
country: United States
state: Missouri
city: Gibbsboro
country: United States
state: New Jersey
city: Buffalo
country: United States
state: New York
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Memphis
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
Study officials:
affiliation: Eisai Limited
name: Michelle Gee
role: STUDY_DIRECTOR
References:
citation: 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.