Trial Outcomes & Findings for 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 (NCT NCT03288129)

Results Overview

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 3 months after the initiation of treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

54 participants

Primary outcome timeframe

Month 3

Results posted on

2022-05-16

Participant Flow

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

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

Participant milestones

Participant milestones
Measure	Perampanel 12 mg During the Titration Period, participants received perampanel 2 milligrams per day (mg/day) and were up-titrated in no less than 2-week intervals in increments of 2 milligram (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.
Overall Study STARTED	54
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Perampanel 12 mg During the Titration Period, participants received perampanel 2 milligrams per day (mg/day) and were up-titrated in no less than 2-week intervals in increments of 2 milligram (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.
Overall Study Adverse Event	10
Overall Study Lost to Follow-up	3
Overall Study Withdrawal by Subject	3
Overall Study Withdrawal of consent/assent	1
Overall Study Other	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Perampanel 12 mg n=54 Participants 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.
Age, Continuous	38.5 years STANDARD_DEVIATION 17.32 • n=99 Participants
Sex: Female, Male Female	27 Participants n=99 Participants
Sex: Female, Male Male	27 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	9 Participants n=99 Participants
Race (NIH/OMB) White	42 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants

PRIMARY outcome

Timeframe: Month 3

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 3 months after the initiation of treatment.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=54 Participants 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.
Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment	85.2 percentage of participants

PRIMARY outcome

Timeframe: Month 6

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 6 months after the initiation of treatment.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=54 Participants 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.
Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment	68.5 percentage of participants

PRIMARY outcome

Timeframe: Month 9

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 9 months after the initiation of treatment.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=54 Participants 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.
Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment	63.0 percentage of participants

PRIMARY outcome

Timeframe: Month 12

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

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

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=54 Participants 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.
Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment	51.9 percentage of participants

SECONDARY outcome

Timeframe: Up to 39 weeks of Maintenance Period

Population: The Full Analysis Set (FAS) included participants who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here "overall number of participants analyzed" signifies participants those who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=52 Participants 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.
Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period	19.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 months of Maintenance Period

Population: The FAS included participants who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here "overall number of participants analyzed" signifies participants those who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=52 Participants 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.
Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period	34.6 percentage of participants

SECONDARY outcome

Timeframe: Up to 6 months of Maintenance Period

Population: The FAS included participants who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here "overall number of participants analyzed" signifies participants those who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=52 Participants 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.
Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period	23.1 percentage of participants

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: The FAS included participants who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here "overall number of participants analyzed" signifies participants those who were evaluable for this outcome measure.

Percentage of participants who received perampanel as a first adjunctive therapy and converted to perampanel monotherapy were reported.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=52 Participants 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.
Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy	28.8 percentage of participants

SECONDARY outcome

Timeframe: From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

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.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=54 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (TEAE)	48 Participants

SECONDARY outcome

Timeframe: From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

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.

Outcome measures

Outcome measures
Measure	Perampanel 12 mg n=54 Participants 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.
Number of Participants With Treatment-emergent Serious Adverse Events (SAE)	4 Participants

Adverse Events

Perampanel 12 mg

Serious events: 4 serious events

Other events: 47 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Perampanel 12 mg n=54 participants at risk 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.
General disorders Sudden unexplained death in epilepsy	1.9% 1/54 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Nervous system disorders Transient ischaemic attack	1.9% 1/54 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Psychiatric disorders Depression	1.9% 1/54 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Psychiatric disorders Mental status changes	1.9% 1/54 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Psychiatric disorders Suicidal ideation	1.9% 1/54 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)

Other adverse events

Other adverse events
Measure	Perampanel 12 mg n=54 participants at risk 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.
Gastrointestinal disorders Nausea	7.4% 4/54 • Number of events 7 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Gastrointestinal disorders Vomiting	11.1% 6/54 • Number of events 6 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
General disorders Fatigue	16.7% 9/54 • Number of events 12 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Infections and infestations Upper respiratory tract infection	5.6% 3/54 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Infections and infestations Nasopharyngitis	9.3% 5/54 • Number of events 6 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Nervous system disorders Balance disorder	5.6% 3/54 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Nervous system disorders Dizziness	27.8% 15/54 • Number of events 19 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Nervous system disorders Headache	9.3% 5/54 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Nervous system disorders Memory impairment	5.6% 3/54 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Nervous system disorders Somnolence	14.8% 8/54 • Number of events 10 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Psychiatric disorders Aggression	5.6% 3/54 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Psychiatric disorders Depression	5.6% 3/54 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Psychiatric disorders Irritability	9.3% 5/54 • Number of events 6 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 3/54 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Infections and infestations Ear infection	7.4% 4/54 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place