Trial Evaluating the Efficacy and Safety of Perampanel Added to Monotherapy in Participants With Partial Onset Seizures With or Without Secondary Generalization

Multicenter, Open-label Trial Evaluating the Efficacy and Safety of Perampanel Added to Monotherapy in Patients With Partial Onset Seizures With or Without Secondary Generalization

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02726074

Enrollment

106

Registered

2016-04-01

Start date

2016-05-03

Completion date

2018-04-26

Last updated

2020-02-05

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

Conditions

Epilepsy

Keywords

epilepsy, partial-onset seizures, secondarily generalized seizures

Brief summary

This is a multi-center, open-label, single-arm, phase 4 study to evaluate the efficacy of perampanel added to monotherapy for partial onset seizures with or without secondarily generalized seizures (total seizures).

Detailed description

This multi-center, open-label, single-arm study evaluating the efficacy of perampanel added to monotherapy for partial onset seizures consists of 2 periods: Titration Period (12 weeks) and Maintenance Period (24 weeks). During the Titration Period, participants will begin receiving perampanel 2 milligrams per day (mg/day) and be up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants will receive the last dose they achieved at the end of the Titration Period and will continue receiving this dose once daily for the remainder of the study.

Interventions

DRUGPerampanel

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

Inclusion criteria

* Have a diagnosis of epilepsy with partial onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981) * Need an initial add-on therapy after failure to control seizures with the first or further monotherapy at the optimal dose and duration * Despite antiepileptic drug (AED) treatment within the last 8 weeks, participants must have had greater than or equal to 2 partial onset seizures, and the interval between those seizures should be more than 24 hours prior to Visit 1 (Week 0). * Are currently being treated with stable doses of monotherapy for 8 weeks prior to Visit 1 (Week 0) (Standard AEDs) * If antidepressants or antianxiety drugs are used, participants must be receiving stable doses and administrations of antidepressants or antianxiety drugs for 8 weeks prior to Visit 1 (Week 0)

Exclusion criteria

* Females who are pregnant (positive beta-human chorionic gonadotropin (β-hCG test) or breastfeeding * Presence of previous history of Lennox-Gastaut syndrome * Presence of nonmotor simple partial seizures only * Presence of primary generalized epilepsies or seizures such as absences and/or myoclonic epilepsies * A history of status epilepticus within 12 weeks before Visit 1 (Week 0) * 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 Visit 1 (Week 0) * 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 \[EEG\]) and benzodiazepines (except for seizure control indication) within 8 weeks prior to Visit 1 (Week 0) * Use of intermittent rescue benzodiazepines (that is, 1 to 2 doses over a 24-hr period considered one-time rescue) 2 or more times in an 8-week period prior to Visit 1 (Week 0) * Participant who is participating in other intervention clinical trial

Design outcomes

Primary

Measure	Time frame	Description
50 Percent (%) Responder Rate for Partial Onset Seizure With or Without Secondary Generalization	Baseline up to Week 36	The 50% responder rate was defined as the percentage of participants who achieved at least 50% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.

Secondary

Measure	Time frame	Description
100% Responder Rate (Seizure Free Rate) for Partial Onset Seizure With or Without Secondary Generalization	Baseline up to Week 36	The 100% responder rate was defined as the percentage of participants who achieved at least 100% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.
Percent Change From Baseline in Partial Onset Seizure Frequency With or Without Secondary Generalization to the Titration and Maintenance Period	Weeks 12 and 36	Percent change in the frequency of partial onset seizure with or without secondary generalization was defined as the percent reduction in seizure frequency from baseline to titration period and maintenance period. Percent change from Baseline was calculated as: (\[post-Baseline value minus the Baseline value\] / Baseline value)\*100. A negative percent change from baseline indicates a decrease in partial seizure frequency.
50% Responder Rate in Secondary Generalized Tonic Clonic (GTC) Seizures	Baseline up to Week 36	The 50% responder rate was defined as the percentage of participants who have achieved at least a 50% reduction from baseline in the frequency of secondary GTC seizure during the Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain.
75% Responder Rate for Partial Onset Seizure With or Without Secondary Generalization	Baseline up to Week 36	The 75% responder rate was defined as the percentage of participants who achieved at least 75% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.
100% Responder Rate (Seizure Free Rate) in Secondary GTC Seizures	Baseline up to Week 36	The 100% responder rate was defined as the percentage of participants who have at least a 100% reduction from baseline in the frequency of secondary GTC seizures during the Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain.
Percent Change From Baseline in Secondary GTC Seizure Frequency to the Titration and Maintenance Period	Weeks 12 and 36	Percent change in the frequency of secondary GTC seizure was defined as the percent reduction in seizure frequency from baseline to Titration Period and Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain. Percent change from Baseline was calculated as: (\[post-Baseline value minus the Baseline value\] / Baseline value)\*100. A negative percent change from baseline indicates a decrease in partial seizure frequency.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)	—
75% Responder Rate in Secondary GTC Seizures	Baseline up to Week 36	The 75% responder rate was defined as the percentage of participants who achieved at least a 75% reduction from baseline in seizure frequency of secondary GTC seizure during the Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain.

Countries

South Korea

Participant flow

Recruitment details

Participants took part in the study at 11 investigative sites in Korea from 03 May 2016 to 26 April 2018.

Pre-assignment details

A total of 106 participants were enrolled in this study, 102 participants were included in the safety set excluding 3 participants who did not received the investigational product and 1 participant who was not assessed for safety at least once after study treatment.

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 according to 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 Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.	102
Total	102

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 according to 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 Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.

102

Total

102

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	14
Overall Study	Lost to Follow-up	2
Overall Study	Others	3
Overall Study	Protocol Violation	3
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	Perampanel 12 mg	—
Age, Continuous	42.25 years STANDARD_DEVIATION 14.26	—
Race and Ethnicity Not Collected	—	— Participants
Sex: Female, Male Female	61 Participants	—
Sex: Female, Male Male	41 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 102
other Total, other adverse events	74 / 102
serious Total, serious adverse events	8 / 102

Outcome results

Primary

50 Percent (%) Responder Rate for Partial Onset Seizure With or Without Secondary Generalization

The 50% responder rate was defined as the percentage of participants who achieved at least 50% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.