Evaluation of the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

An Open-Label Extension Phase of the Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Studies to Evaluate the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

The purpose of this study was to evaluate the safety and tolerability of perampanel (up to 12 mg/day) given as adjunctive treatment in subjects with refractory partial seizures and to evaluate the maintenance of effect of perampanel for the control of refractory partial seizures.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: perampanel

Detailed Description

This was an open-label extension (OLE) study for subjects who completed one of the following double-blind, placebo-controlled, Phase 3 studies: E2007-G000-304 (NCT00699972), E2007-G000-305 (NCT00699582), and E2007-G000-306 (NCT00700310). This OLE study consisted of 2 phases: an Open-label Treatment Phase (comprised of a 16-week blinded Conversion Period and a 256-week Maintenance Period) and a Follow-up Phase (4 weeks). During the Conversion Period, subjects and investigators remained blinded to the treatment received in the previous DB study. To achieve this, all subjects continued to take 6 tablets of study medication (2 mg perampanel or matching placebo) or fewer as they were instructed during the core Double-Blind (DB) study. During the open-label Maintenance Period, subjects were treated with the perampanel dose that provided the best combination of individual efficacy and tolerability.

• Study Type: Interventional
• Enrollment (Actual): 1218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1406FWY
  • Capital Federal, Argentina, 1428
  • Ciudad Autonoma de Buenos Aires, Argentina, C1280AEB
  • Ciudad Autonoma de Buenos Aires, Argentina, C1117ABE
  • Ciudad Autonoma de Buenos Aires, Argentina, C1122AAK
  • Ciudad Autonoma de Buenos Aires, Argentina, C1182ACD
  • Ciudad Autonoma de Buenos Aires, Argentina, C1221ADC
  • Cordoba, Argentina, X5000JJS
  • Cordoba, Argentina, X5010AOC
  • Guaymallen, Argentina, M5519FNF
  • La Plata, Buenos Aires, Argentina, B1902AHD
  • Lanus Oeste, Buenos Aires, Argentina, B1824CWE
  • Rosario, Argentina, S2000DSV
  • Salta, Argentina, A4402AYT
  • Tucuman, Argentina, T4000DVD
• Australia
  • South Australia
    • Woodville, South Australia, Australia, 5011
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
    • Heidelberg, Victoria, Australia, 3084
    • Parkville, Victoria, Australia, 3050
• Austria
  • Graz, Austria, 8036
  • Innsbruck, Austria, 6020
  • Linz, Austria, A-4021
• Belgium
  • Bruxelles, Belgium, 1070
  • Leuven, Belgium, 3000
  • Ottignies, Belgium, 1340
• Bulgaria
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria, 4002
  • Sofia, Bulgaria, 1606
  • Sofia, Bulgaria, 1113
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
  • Ontario
    • London, Ontario, Canada, N6A 5A5
    • Toronto, Ontario, Canada, M5B 1T9
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
• Chile
  • Santiago, Chile, 8900085
  • Santiago, Chile, 3459
  • Santiago, Chile, 8260094
  • Valdivia, Chile, 5090145
• China
  • Beijing, China, 100730
  • Chengdu, China, 610041
  • Chongqing, China, 400016
  • Shanghai, China, 200040
• Czech Republic
  • Olomouc, Czech Republic, 775 20
  • Praha 4, Czech Republic, 140 59
  • Praha 5, Czech Republic, 150 06
• Estonia
  • Tallinn, Estonia, EE-13419
  • Tartu, Estonia, EE-51014
• Finland
  • Kuopio, Finland, FI-70210
  • Tampere, Finland, FI-33520
• France
  • Bethune, France, 62408
  • Bron, France, 69677
  • Montpellier, France, 34295
  • Rennes, France, 35033
  • Toulouse, France, 31059
• Germany
  • Berlin, Germany, 10117
  • Bernau, Germany, 16321
  • Bielefeld, Germany, 33617
  • Bonn, Germany, 53127
  • Dusseldorf, Germany, 40212
  • Erlangen, Germany, 91054
  • Gottingen, Germany, 37075
  • Kehl-Kork, Germany, 77694
  • Mainz, Germany, 55131
  • Marburg, Germany, 35039
  • Munchen, Germany, 81377
  • Ulm, Germany, 89081
  • Westerstede, Germany, 26655
• Greece
  • Thessaloniki, Greece, 546 36
  • Thessaloniki, Greece, 57010
• Hong Kong
  • Hong Kong, Hong Kong
  • Kowloon, Hong Kong
  • Pokfulam, Hong Kong, 852
  • Shatin, Hong Kong
• Hungary
  • Budapest, Hungary, 1145
  • Budapest, Hungary, 1097
  • Budapest, Hungary, 1136
  • Budapest, Hungary, H-1143
  • Kecskemet, Hungary, 6000
• India
  • Hyderabad, India, 500082
  • Hyderabad, India, 500001
  • Jaipur, India, 302004
  • Mangalore, India, 575002
  • Mumbai, India, 400026
  • Nagpur, India, 440010
  • Nasik, India, 422004
  • New Delhi, India, 110060
  • Pune, India, 411030
  • Pune, India, 411011
  • Visakhapatnam, India, 530002
• Israel
  • Ashkelon, Israel, 78278
  • Haifa, Israel, 31096
  • Holon, Israel, 58100
  • Kfar Saba, Israel, 44281
  • Petach Tikva, Israel, 49202
  • Ramat Gan, Israel, 52621
• Italy
  • Firenze, Italy, 50134
  • Genova, Italy, 16147
  • Milano, Italy, 20133
  • Milano, Italy, 20121
  • Napoli, Italy, 80131
• Korea, Republic of
  • Busan, Korea, Republic of, 614735
  • Daegu, Korea, Republic of, 700712
  • Pusan, Korea, Republic of, 602715
  • Seoul, Korea, Republic of, 110744
  • Seoul, Korea, Republic of, 138736
  • Seoul, Korea, Republic of, 135710
  • Seoul, Korea, Republic of, 120752
• Latvia
  • Riga, Latvia, LV-1038
  • Riga, Latvia, LV-1004
  • Valmiera, Latvia, LV-4201
• Lithuania
  • Kaunas, Lithuania, LT-50009
  • Klaipeda, Lithuania, LT-92288
  • Vilnius, Lithuania, LT-08661
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
  • Kuala Terengganu, Malaysia, 20400
• Mexico
  • Aguascalientes, Mexico, 20127
  • Mexico City, Distrito Federal, Mexico, 14050
  • Monterrey, Nuevo Leon, Mexico, 64000
  • San Luis Potosi, Mexico, 78240
• Netherlands
  • Heeze, Netherlands, 5591 VE
  • Zwolle, Netherlands, 8025 BV
• Philippines
  • Ermita, Philippines, 1000
  • Makati City, Philippines, 1229
• Poland
  • Bialystok, Poland, 15-276
  • Gdansk, Poland, 80-803
  • Gdansk, Poland, 80-952
  • Katowice, Poland, 40-635
  • Lublin, Poland, 20-718
  • Warszawa, Poland, 02-957
• Portugal
  • Coimbra, Portugal, 3000-075
  • Lisboa, Portugal, 1649-035
  • Porto, Portugal, 4200-319
• Romania
  • Bucharest, Romania
  • Bucharest, Romania, 20125
• Russian Federation
  • Ekaterinburg, Russian Federation, 620149
  • Kazan, Russian Federation, 420097
  • Moscow, Russian Federation, 119992
  • Moscow, Russian Federation, 107076
  • Moscow, Russian Federation, 107066
  • Moscow, Russian Federation, 125412
  • Nizhniy Novgorod, Russian Federation, 603005
  • Omsk, Russian Federation, 644001
  • Samara, Russian Federation, 443095
  • Smolensk, Russian Federation, 214018
  • Tyumen, Russian Federation, 625039
  • Yaroslavl, Russian Federation, 150030
• Serbia
  • Belgrade, Serbia, 11000
  • Nis, Serbia, 18000
  • Novi Sad, Serbia, 21000
• South Africa
  • Cape Town, South Africa, 7500
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
• Spain
  • Andalucia
    • Granada, Andalucia, Spain, 18012
  • Cataluna
    • Badalona, Cataluna, Spain, 8916
    • Barcelona, Cataluna, Spain, 8003
    • Barcelona, Cataluna, Spain, 8025
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46009
  • Madrid, Communidad de
    • Alcorcon, Madrid, Communidad de, Spain, 28922
    • Madrid, Madrid, Communidad de, Spain, 28040
  • Pais Vasco
    • Baracaldo, Pais Vasco, Spain, 48903
• Sweden
  • Goteborg, Sweden
  • Linkoping, Sweden
• Taiwan
  • Kaohsiung, Taiwan, 833
  • Taichung, Taiwan, 40705
  • Tainan, Taiwan, 70403
  • Taoyuan, Taiwan, 333
• Thailand
  • Bangkok, Thailand, 10400
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330
  • Chiangmai, Thailand, 50200
  • Muang, Thailand, 40002
• Ukraine
  • Donetsk, Ukraine, 83114
  • Donetsk, Ukraine, 83052
  • Kharkiv, Ukraine, 61068
  • Kharkiv, Ukraine, 61018
  • Kyiv, Ukraine, 4209
  • Kyiv, Ukraine, 4080
  • Lviv, Ukraine, 79010
  • Uzhgorod, Ukraine, 88000
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
  • London, United Kingdom, SW17 0QT
  • Middlesbrough, United Kingdom, TS4 3BW
  • Stoke-on-Trent, United Kingdom, ST4 7LN
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arizona
    • Phoenix, Arizona, United States, 85013
    • Phoenix, Arizona, United States, 85004
    • Tucson, Arizona, United States, 85724
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Fresno, California, United States, 93710
    • San Francisco, California, United States, 94115
    • Ventura, California, United States, 93003
  • Colorado
    • Denver, Colorado, United States, 80218
    • Fort Collins, Colorado, United States, 80525
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
  • Florida
    • Gulf Breeze, Florida, United States, 32561
    • Jacksonville, Florida, United States, 32209
    • Jacksonville, Florida, United States, 32224
    • Orlando, Florida, United States, 32819
    • Tallahassee, Florida, United States, 32308
    • Tampa, Florida, United States, 33609
  • Georgia
    • Atlanta, Georgia, United States, 30342
    • Suwanee, Georgia, United States, 30024
  • Idaho
    • Boise, Idaho, United States, 83702
  • Indiana
    • Indianapolis, Indiana, United States, 46256
  • Iowa
    • Ames, Iowa, United States, 50010
  • Kentucky
    • Lexington, Kentucky, United States, 40536
  • Louisiana
    • Houma, Louisiana, United States, 70363
  • Maryland
    • Baltimore, Maryland, United States, 21287-7247
    • Bethesda, Maryland, United States, 20817
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
  • Missouri
    • Chesterfield, Missouri, United States, 63017
    • Kansas City, Missouri, United States, 64111
    • Saint Louis, Missouri, United States, 63110
  • New York
    • Albany, New York, United States, 12208
    • Buffalo, New York, United States, 14222
    • Great Neck, New York, United States, 11021
    • Lawrence, New York, United States, 11559
    • New York, New York, United States, 10016
    • Rochester, New York, United States, 14642
    • Syracuse, New York, United States, 13210
  • North Carolina
    • Asheville, North Carolina, United States, 28806
  • Ohio
    • Akron, Ohio, United States, 44308
    • Cincinnati, Ohio, United States, 45219
    • Columbus, Ohio, United States, 43221
    • Toledo, Ohio, United States, 43614
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137
  • Oregon
    • Portland, Oregon, United States, 97210
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19107
  • South Carolina
    • Charleston, South Carolina, United States, 29425
  • Tennessee
    • Memphis, Tennessee, United States, 38105
  • Texas
    • Dallas, Texas, United States, 75230
    • Dallas, Texas, United States, 75235
    • Dallas, Texas, United States, 75251
    • El Paso, Texas, United States, 79905
    • Houston, Texas, United States, 77030
  • Utah
    • Salt Lake City, Utah, United States, 84108
  • Virginia
    • Richmond, Virginia, United States, 23298
  • Washington
    • Seattle, Washington, United States, 98104
  • Wisconsin
    • Madison, Wisconsin, United States, 53715

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Each participant who met the following criteria were enrolled in this study:

1. Who completed Visit 8 of study E2007-G000-304, E2007-G000-305, or E2007-G000-306 and complied with the inclusion and exclusion criteria for that study (excluding criteria that are related to seizure occurrences).
2. Provided written informed consent signed by participant or legal guardian prior to entering the study or undergoing any study procedures (If the written informed consent was provided by the legal guardian because the participant was unable to do so, a written or verbal assent from the participant was obtained).
3. Who was considered reliable and willing to be available for the study period and record seizures and report adverse events them self or have a caregiver who can record and report the events for them.
4. Females who were either of non-childbearing potential (defined as having undergone surgical sterilization, or postmenopausal [>age 50 and amenorrheic for 12 months]) or of childbearing potential. Females of childbearing potential were enrolled only if they agreed to be abstinent or continue using at least 1 medically acceptable method of contraception (eg, a double-barrier method [eg, condom + spermicide, condom + diaphragm with spermicide], IUD, or have a vasectomised partner) throughout the study period and for 2 months after the last dose of study drug. Women using hormonal contraceptives were required to use an additional approved method of contraception (as described previously) continuously throughout the entire study period and for 2 months after the last dose of study drug. (It was not required for male subjects to use contraceptive measures based on preclinical toxicology data).
5. Continued to be treated with a stable dose of 1 or a maximum of 3 approved anti-epileptic drugs.

Exclusion Criteria:

Participants who met the following criteria were excluded from the study:

1. Those who, for any reason, discontinued early from the preceding double-blind study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Perampanel; Participants previously receiving perampanel/placebo in the double blind-study, were titrated to receive perampanel 2 mg to 12 mg, once daily in the Open-Label Extension (OLE) study up to approximately 5 years.	Drug: perampanel; Perampanel 2 mg to 12 mg, once daily in the Open-Label Extension (OLE) study up to approximately 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Non-Serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs)	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A SAE was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (ie, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was as a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). In this study, treatment emergent AEs (defined as an AE (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.	From date of first dose of perampanel up to 30 days after the last dose of perampanel or up to approximately 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline.	Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The seizure frequency per 28 days was calculated as the number of seizures divided by the number of days in the interval and multiplied by 28. The percent change in 28-day seizure frequency from pre-perampanel baseline was assessed for all partial-onset seizure types. The pre-perampanel baseline was defined as: (1) for participants who had been assigned to placebo treatment in the core DB study, the pre-perampanel baseline was computed from all data during the core DB study, and (2) for participants who had been assigned to perampanel in the core DB study, the pre-perampanel baseline was computed from the pre-randomization phase of the core DB study.	Pre-perampanel Baseline and Weeks (1-13, 14-26, 27-39, 40-52, 53-65, 66-78, 79-91, 92-104, 105-117, 118-130, 131-143, 144-156, 157-169, 170-182, 183-195, 196-208, 209-221, 222-234, 235-247, and 248-260)
Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-Perampanel Baseline.	Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The percentage of participants who experienced a 50% or greater reduction in seizure frequency per 28 days relative to the pre-perampanel Baseline(responders) was assessed. The pre-perampanel baseline was defined as: (1) for participants who had been assigned to placebo treatment in the core DB study, the Pre-perampanel baseline was computed from all data during the core Double-Blind (DB) study, and (2) for participants who had been assigned to perampanel in the core DB study, the pre-perampanel baseline was computed from the pre-randomization phase of the core DB study. The data is presented as percent responders.	Pre-perampanel Baseline and Weeks (1-13, 14-26, 27-39, 40-52, 53-65, 66-78, 79-91, 92-104, 105-117, 118-130, 131-143, 144-156, 157-169, 170-182, 183-195, 196-208, 209-221, 222-234, 235-247, 248-260)

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Michelle Gee, PhD., Eisai Limited

Publications and helpful links

General Publications

• Maguire M. Response to "Perampanel and pregnancy: Could experience be a gloomy lantern that does not even illuminate its bearer?". Epilepsy Behav. 2022 Apr;129:108654. doi: 10.1016/j.yebeh.2022.108654. Epub 2022 Mar 16. No abstract available.
• Rosenfeld W, Conry J, Lagae L, Rozentals G, Yang H, Fain R, Williams B, Kumar D, Zhu J, Laurenza A. Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study. Eur J Paediatr Neurol. 2015 Jul;19(4):435-45. doi: 10.1016/j.ejpn.2015.02.008. Epub 2015 Mar 5.
• Krauss GL, Perucca E, Kwan P, Ben-Menachem E, Wang XF, Shih JJ, Patten A, Yang H, Williams B, Laurenza A. Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open-label extension of phase III randomized trials: Study 307. Epilepsia. 2018 Apr;59(4):866-876. doi: 10.1111/epi.14044. Epub 2018 Mar 25.
• Krauss GL, Perucca E, Ben-Menachem E, Kwan P, Shih JJ, Clement JF, Wang X, Bagul M, Gee M, Zhu J, Squillacote D. Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307. Epilepsia. 2014 Jul;55(7):1058-68. doi: 10.1111/epi.12643. Epub 2014 May 27.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: August 13, 2008
• First Submitted That Met QC Criteria: August 13, 2008
• First Posted (Estimate): August 14, 2008

Study Record Updates

• Last Update Posted (Estimate): March 14, 2016
• Last Update Submitted That Met QC Criteria: February 11, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Partial onset seizures
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures
• Other Study ID Numbers: E2007-G000-307