The study being done to see if the Study Drug is safe, tolerable, and can help control seizure in children with epilepsy who are aged 4 to less than 12 years of age and who are already taking seizure medications. The study will also look at pharmacokinetics, which is used to find out the concentration of perampanel in your child’s blood over a period of time.

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2014-002167-16-HU
• Date of registration: 12/12/2016
• Prospective Registration: Yes
• Primary sponsor: Eisai Limited
• Public title: The study being done to see if the Study Drug is safe, tolerable, and can help control seizure in children with epilepsy who are aged 4 to less than 12 years of age and who are already taking seizure medications. The study will also look at pharmacokinetics, which is used to find out the concentration of perampanel in your child’s blood over a period of time.
• Scientific title: An Open-Label, Multicenter Study with an Extension Phase to Evaluate the Safety, Tolerability, and Exposure-Efficacy Relationship of Perampanel Oral Suspension when Administered as an Adjunctive Therapy in Pediatric Subjects (Age 4 to less than 12 years) with Inadequately Controlled Partial-Onset Seizures or Primary Generalized Tonic-Clonic Seizures
• Date of first enrolment: 30/01/2017
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002167-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, France, Hungary, Italy, Japan, Korea, Republic of, Latvia, Poland, Spain, United States

Contacts

• Name: Medical Information
• Affiliation: Eisai Europe Ltd.

• Name: Medical Information
• Affiliation: Eisai Europe Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have a diagnosis of epilepsy with POS with or without secondarily generalized seizures or PGTC 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 EEG that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history)
2. Male or female subject, from age 4 to less than 12 years at the time of informed consent/assent
3. Have a minimum weight of 16 kg (35 lb)
4. Have had a brain imaging (eg, magnetic resonance imaging [MRI] scan or computed tomography[CT]) before Visit 1 that ruled out a progressive cause of epilepsy
5. During the 4 weeks ± 3 days before Visit 2, subjects must have had equal or greater than 1 POS or 1 PGTC seizure. Only simple POS with motor signs, complex POS, and complex POS with secondary generalization are counted toward this inclusion for POS.
6. Are currently being treated with stable doses of 1 to a maximum of 2 approved AEDs. Doses must be stable for at least 4 weeks before to Visit 1; in the case where a new AED regimen has been initiated for a subject, the dose must be stable for at least 8 weeks prior to Visit 1. Only 1 EIAED (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of 2 AEDs is allowed (A vagal nerve stimulator [VNS] will be counted as one of the 2 allowed AEDs).
Are the trial subjects under 18? yes
Number of subjects for this age range: 160
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive [ß-hCG] or [hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained >72 hours before the 1st dose of study drug.
2. Females of childbearing potential who:
• Had unprotected sexual intercourse within 30 days before study entry & who do not agree to use a highly effective method of contraception ( total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation. If a highly effective method is not appropriate or acceptable for the subject, then the subject may use a medically effective method (a double barrier method such as condom plus diaphragm with spermicide).
• Are currently abstinent & do not agree to use a double-barrier method (as above) or refrain from sexually active during the study period or for 28 days after study drug discontinuation.
• Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing & who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation.
3. Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before Visit 1.
4. Have a history of status epilepticus that required hospitalization during the 6 months before to Visit 1.
5. Have an unstable psychiatric diagnosis that may confound subjects’ ability to participate the study or that may prevent completion of the protocol specified tests (significant suicide risk, including suicidal behavior & ideation within 6 months before Visit 1, current psychotic disorder, acute mania).
6. Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (ie answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS) in subjects aged > 6 years.
7. 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.
8. Evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigators could affect the subject’s safety or interfere with the study assessments.
9. Severe renal insufficiency
10. Evidence of significant active hepatic disease. Stable elevation of liver enzymes, ALT & AST due to concomitant medication(s), will be allowed if they are less than 3 times the ULN.
11. Evidence of significant active hematological disease;WBC count = 2500/µL (2.50 1E+09/L) or an absolute neutrophil count = 1000/µL (1.00 1E+09/L).
12. Clinically significant ECG abnormality, including prolonged corrected QT interval defined as > 450 msec.
13. Have a progressive central nervous system disease, including degenerative CNS diseases & progressive tumors.
14. Multiple drug allergies or a severe drug reaction to an AEDs, including dermatological (Stevens-Johnson syndrome) haematological or organ toxicity.
15. Concomitant use of felbamate as an AED for < 2 years or where the dose has not been stable for at least 8 weeks before Visit 1. They must not have a history of WBC count below = 2500/µL (

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Epilepsy : 1) Partial-Onset Seizures (POS) 2) Primary Generalized Tonic-Clonic Seizures (PGTC)
MedDRA version: 19.0 Level: HLT Classification code 10018101 Term: Generalised tonic-clonic seizures System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0 Level: PT Classification code 10061334 Term: Partial seizures System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Fycompa
Product Name: Perampanel
Product Code: E2007
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Perampanel
CAS Number: 380917-97-5
Current Sponsor code: E2007
Other descriptive name: Perampanel
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At the end of the core phase and the extension phase

Main Objective: To evaluate the safety and tolerability of perampanel oral suspension when administered as an adjunctive therapy in children (ages 4 to <12 years) with inadequately controlled partial-onset seizures (POS) or primary generalized tonic-clonic seizures (PGTC)

Primary end point(s): Safety and tolerability, which include incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), laboratory parameters, vital signs, and ECG parameters, of perampanel oral suspension in children (ages 4 to <7 years and =7 years to <12 years) with POS or PGTC

Secondary Objective: 1. Characterize PK of perampanel & the relationship between perampanel plasma concentrations, efficacy & safety using population PK/PD modeling
2. Evaluate effects of perampanel on cognition, behavior, visuomotor skills & growth & development in children during short-term (23 wks) & long-term (up to 52 wks) treatment
3. Evaluate frequency of EEG abnormalities during awake & sleep state during 52 wks of treatment
4. Evaluate suicidal ideation & suicidal behavior in children 6 yrs to less than 12 yrs as measured by the C-SSRS during 52 wks of treatment
5. Evaluate efficacy of perampanel as measured by the median percent change per 28 days in seizure frequency by the proportion of responders (=25%, =50% & =75%) & by the proportion of subjects who are seizure-free for POS, PGTC, & GTC seizures
6. Evaluate, in Japanese subjects, efficacy of perampanel on POS in this study compared to Pbo in Study
E2007-J000-335
7. Assess effects of perampanel on the CGI, CGIS & CGIC

Secondary Outcome(s)

Secondary end point(s): 1. The relationship between plasma levels of perampanel and efficacy endpoints (ie, change in average seizure frequency over 28 days, responder probability, and the proportion of subjects who are seizure-free in the Maintenance Period of the Core Study) separately for each seizure type
2. The relationship between plasma levels of perampanel and cognition endpoints including change from baselines in ABNAS, CBCL, and LGPT. In addition, depending on the AE data, the relationship between plasma levels of perampanel and select AEs will be assessed.
3. Change from baseline at Week 23 and Week 52 in ABNAS, CBCL, and LGPT
4. Changes from baseline at Week 23 and Week 52 in growth and development parameters (height, weight, thyroid, and IGF-1)
5. Change from baseline in EEG and the frequency of EEG abnormalities during awake and sleep state
6. Proportion of subjects (aged 6 or older at time of consent/assent) with any treatment-emergent reports of suicidal ideation and behavior on the C-SSRS and intensity of these behaviors assessed using C-SSRS scores
7. The median percent change in seizure frequency per 28 days during Treatment Phase (Titration Period and Maintenance Period) of the Core Study, and during the long-term treatment (up to 52 weeks) relative to the Pretreatment Phase. Seizure frequency will be based on the number of seizures per 28 days, calculated as the number of seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.
8. Proportion of responders (25% responders defined as a decrease in 28-day seizure frequency of equal or greater than 25% compared to baseline seizure frequency; 50% responders defined as a decrease in 28-day seizure frequency of equal or greater than 50% compared to baseline seizure frequency; 75% responders defined as a decrease in 28-day seizure frequency of equal or greater than 75% compared to baseline seizure frequency) during Maintenance Period of Core Study, and during the long term treatment (up to 52 weeks)
9. Proportion of subjects who are seizure-free during Maintenance Period of Core Study, and during the long term treatment (up to 52 weeks)
10. CGI of Change

Timepoint(s) of evaluation of this end point: At the end of the core phase and the extension phase

Secondary ID(s)

E2007-G000-311

Source(s) of Monetary Support

Eisai Inc.

Ethics review

Status: Approved
Approval date: 26/01/2017
Contact: