Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures

Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03288129

Enrollment

Registered

2017-09-19

Start date

2017-08-23

Completion date

2021-04-27

Last updated

2022-05-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, Secondarily Generalized Seizures

Keywords

monotherapy, adjunctive therapy, open-label, multicenter

Brief summary

This study will assess the retention rate of perampanel when given as monotherapy or first adjunctive therapy in participants with partial-onset seizures or primary generalized tonic clonic seizures. The study consists of 4 periods: a Screening Period (to start no earlier than 6 weeks before the first dose of study drug), a Titration Period (up to 13 weeks), a Maintenance Period (39 weeks), and a Follow-Up Period (4 weeks).

Interventions

DRUGPerampanel

film-coated tablets

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

4 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participants will be male or female and no younger than 4 years of age and be able to swallow perampanel tablets. * Participants must have a diagnosis of epilepsy with POS with or without SGS or with PGTCS. Either of the following must have occurred to support an epilepsy diagnosis: 1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart 2. One unprovoked (or reflex) seizure with Electroencephalography (EEG) evidence of seizures * Participants who receive perampanel as a first adjunctive therapy must currently have been treated with stable doses of monotherapy with an anti-epileptic drug (AED) for 8 weeks prior to Visit 2 (Week 0), have not previously received adjunctive AED treatment, and must, in the investigator's judgement, be in need of initial adjunctive therapy after failure to control seizures with AED monotherapy, at the optimal dose and duration. * Participants who receive perampanel as monotherapy, who were newly diagnosed (treatment naïve), following the defined diagnosis of epilepsy. * Participants who are currently receiving monotherapy treatment may receive perampanel as monotherapy if, in the investigator's judgment, the participant may benefit from a change in monotherapy treatment. Participants must not have previously received adjunctive AED treatment. * If antidepressants or antianxiety drugs are used, participants must be on a stable dose regimen of these drugs during the 8 weeks before Visit 2 (Week 0).

Exclusion criteria

* Participants should not have previously received or currently be receiving perampanel. * Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin \[β-hCG\] or 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: * Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: * Total abstinence (if it is their preferred and usual lifestyle) * An intrauterine device or intrauterine hormone-releasing system * An oral contraceptive (with additional barrier method if using contraceptive containing levonorgestrel); participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation * Have a vasectomized partner with confirmed azoospermia * Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation For sites outside of the European Union, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, i.e, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide. NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). * Presence of or previous history of Lennox-Gastaut syndrome * Presence of non-motor simple partial seizures only * A history of status epilepticus within 1 year before Screening Visit (Visit 1) * Participants on antipsychotics or who have psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of attempted suicide within 1 year before Screening Visit (Visit 1) * Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors * Concomitant use of barbiturates (except for seizure control indication and premedication for electroencephalogram) and benzodiazepines (except for seizure control indication) within 8 weeks prior to Visit 2 (Week 0) * Use of intermittent rescue benzodiazepines (i.e, 1 to 2 doses over a 24-hour period is considered a one time rescue) 2 or more times in the 8-week period prior to Visit 2 (Week 0) * Severe renal insufficiency (defined by estimated glomerular filtration rate of \< 30 milliliters per minute \[mL/min\]) or participants who receive hemodialysis * Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the participant's safety or study conduct NOTE: Stable elevation of liver enzymes, alanine aminotransferase and aspartate aminotransferase due to concomitant medication(s) will be allowed if they are less than 3 times the upper limits of normal. * Hypersensitivity to perampanel or any excipients * Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption * Participants who are participating in other interventional clinical trial * Participant who are judged to have inadequate cognitive ability for participation in the study (intelligence quotient \< 80 or investigator judgment) * Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of screening, as indicated by answering Yes to questions 4 and 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS) * Any lifetime suicidal behavior based on the C-SSRS * Concomitant use of any form of cannabidiol (CBD) * Planned brain surgery during study participation

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment	Month 3	The retention rate was defined as the percentage of participants remaining on perampanel treatment at 3 months after the initiation of treatment.
Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment	Month 6	The retention rate was defined as the percentage of participants remaining on perampanel treatment at 6 months after the initiation of treatment.
Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment	Month 9	The retention rate was defined as the percentage of participants remaining on perampanel treatment at 9 months after the initiation of treatment.
Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment	Month 12	The retention rate was defined as the percentage of participants remaining on perampanel treatment at 12 months after the initiation of treatment.

Secondary

Measure	Time frame	Description
Number of Participants With Treatment-emergent Adverse Events (TEAE)	From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)	A TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.
Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period	Up to 39 weeks of Maintenance Period	Seizure-free status was defined as no incidence of seizure during the entire maintenance period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participants does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.
Number of Participants With Treatment-emergent Serious Adverse Events (SAE)	From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)	A SAE was defined as any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect. A TEAE was defined as an event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.
Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period	Up to 3 months of Maintenance Period	Seizure-free status was defined as no incidence of seizure at 3 months during the Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.
Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period	Up to 6 months of Maintenance Period	Seizure-free status was defined as no incidence of seizure at 6 months during Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.
Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy	Up to 52 weeks	Percentage of participants who received perampanel as a first adjunctive therapy and converted to perampanel monotherapy were reported.

Countries

United States

Participant flow

Recruitment details

Participants took part in the study at 14 investigative sites in the United States from 23 August 2017 to 27 April 2021.

Pre-assignment details

A total of 68 participants were screened, of which 54 were treated with perampanel.

Participants by arm

Arm	Count
Perampanel 12 mg During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg were allowed based on the participants response and tolerability and at the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to 39 weeks.	54
Total	54

Arm

Count

Perampanel 12 mg

During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg were allowed based on the participants response and tolerability and at the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to 39 weeks.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	10
Overall Study	Lost to Follow-up	3
Overall Study	Other	5
Overall Study	Withdrawal by Subject	3
Overall Study	Withdrawal of consent/assent	1

Baseline characteristics

Characteristic	Perampanel 12 mg
Age, Continuous	38.5 years STANDARD_DEVIATION 17.32
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	9 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	42 Participants
Sex: Female, Male Female	27 Participants
Sex: Female, Male Male	27 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 54
other Total, other adverse events	47 / 54
serious Total, serious adverse events	4 / 54

Outcome results

Primary

Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 12 months after the initiation of treatment.

Time frame: Month 12