Perampanel as Adjunctive Therapy in Pediatrics With Partial Onset Seizures or Primary Generalized Tonic Clonic Seizures

• Status: Active, not recruiting
• Trial end date: 2021-12-17
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, multicenter study with an Extension Phase to evaluate the safety and tolerability of perampanel oral suspension when administered as an adjunctive therapy in children (ages 4 to less than [<] 12 years) with inadequately controlled partial onset seizures (POS) or primary generalized tonic clonic (PGTC) seizures.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eisai Inc.

Criteria

Inclusion Criteria:

• Have a diagnosis of epilepsy with POS with or without secondarily generalized (SG) seizures or PGTC seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981). A diagnosis should have been established at least 6 months prior to Visit 1 by clinical history and an electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (that is, clinical history)

• Male or female participant, from age 4 to <12 years at the time of informed consent/assent

• Have a minimum weight of 16 kilograms (kg) (35 pounds [lb])

• Have had a brain imaging (example, magnetic resonance imaging [MRI] scan or computed tomography [CT] before Visit 1 that ruled out a progressive cause of epilepsy)

• During the 12 weeks +/- 3 days (4 weeks +/- 3 days in Japan only) prior to Visit 2, participants must have equal or greater than (=>) one POS or one PGTC seizure. Only simple POS with motor signs, complex POS, and complex POS with secondary generalization are counted toward this inclusion for POS

• Are currently being treated with stable doses of 1 to a maximum of 3 approved antiepileptic drugs (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 participant, the dose must be stable for at least 8 weeks prior to Visit 1. Only one EIAED (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of three AEDs is allowed (A vagal nerve stimulator [VNS] will be counted as one of the 3 allowed AEDs)

Exclusion Criteria:

• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin [β-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International Units per liter [IU/L] or equivalent units of β-hCG or hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug

• Females of childbearing potential who:

• Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (example, 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 participant, then the participant may use a medically effective method (example, a double barrier method such as condom plus diaphragm with spermicide)

• Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from being 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 and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation

• Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before Visit 1

• Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1

• Have an unstable psychiatric diagnosis that may confound participants' ability to participate in the study or that may prevent completion of the protocol-specified tests (example, significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1, current psychotic disorder, acute mania)

• Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale [C-SSRS]) in participants aged 6 and above

• 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

• Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments

• Evidence of moderate or severe renal insufficiency as defined by estimated glomerular filtration rates (eGFRs) of 31 to <60 milliliters per minute (mL/min) and <30 mL/min, respectively

• 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)

• Evidence of significant active hematological disease; white blood cell (WBC) count equal or less than (=<) 2500 per (/) microliter (µL) (2.50 1 constant [E]+09/liter [L]) or an absolute neutrophil count =<1000/µL (1.00 1E+09/L)

• Clinically significant electrocardiogram (ECG) abnormality, including prolonged corrected QT interval (QTc) defined as greater than (>) 450 milliseconds (msec)

• Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors

• Multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (example, Stevens Johnson syndrome), hematological, or organ toxicity reactions.

• 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. Participants must not have a history of WBC count =<2500/µL, platelets below 100,000, liver function tests (LFTs) above 3 times the 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 before Visit 1 to be eligible for study participation

• Concomitant use of vigabatrin: participants who took vigabatrin in the past must be off vigabatrin for at least 5 months before Visit 1 and with documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in a visual perimetry test

• Concomitant use of cannabinoids

• Used benzodiazepines for epilepsy during which the dose has not been stable for >4 weeks prior to Visit 1. Benzodiazepines use as rescue medication for seizure control is allowed; however, intermittent use of benzodiazepines for any other indication (example, anxiety/sleep disorders) is prohibited

• A VNS implanted <5 months before Visit 1 or changes in parameter <4 weeks before Visit 1 (or thereafter during the study)

• On a ketogenic diet for which the diet is not a stable regimen for at least 4 weeks before Visit 1

• History of or a concomitant medical condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study or compromise the participant's ability to safely complete the study

• Have previously been exposed to perampanel in a clinical trial or by prescription for more than 2 months or discontinued for Adverse Events (AEs)

• 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

• Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption