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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Drug: Perampanel


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perampanel 12 mg<br>During the Titration Period, participants will receive 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. | Drug: Perampanel<br> <br> * Other names: E2007;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline up to Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 75% Responder Rate for Partial Onset Seizure With or Without Secondary Generalization | 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. | Baseline up to Week 36 | 
| 100% Responder Rate (Seizure Free Rate) for Partial Onset Seizure With or Without Secondary Generalization | 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. | Baseline up to Week 36 | 
| Percent Change From Baseline in Partial Onset Seizure Frequency With or Without Secondary Generalization to the Titration and Maintenance Period | 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. | Weeks 12 and 36 | 
| 50% Responder Rate in Secondary Generalized Tonic Clonic (GTC) Seizures | 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. | Baseline up to Week 36 | 
| 75% Responder Rate in Secondary GTC Seizures | 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. | Baseline up to Week 36 | 
| 100% Responder Rate (Seizure Free Rate) in Secondary GTC Seizures | 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. | Baseline up to Week 36 | 
| Percent Change From Baseline in Secondary GTC Seizure Frequency to the Titration and Maintenance Period | 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. | Weeks 12 and 36 | 
| 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
epilepsy, partial-onset seizures, secondarily generalized seizures