Clinical trial NCT00735397: Evaluation of the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Partial onset seizures
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2008-08-14
Enrollment: 1218
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Non-Serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: From date of first dose of perampanel up to 30 days after the last dose of perampanel or up to approximately 5 years.
Secondary outcomes:
measure: Median Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline.
timeFrame: 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)
measure: Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-Perampanel Baseline.
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Fresno
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Ventura
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Fort Collins
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Gulf Breeze
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Suwanee
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Indianapolis
country: United States
state: Indiana
city: Ames
country: United States
state: Iowa
city: Lexington
country: United States
state: Kentucky
city: Houma
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Hattiesburg
country: United States
state: Mississippi
city: Chesterfield
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Albany
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Great Neck
country: United States
state: New York
city: Lawrence
country: United States
state: New York
city: New York
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state: New York
city: Rochester
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city: Syracuse
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state: New York
city: Asheville
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state: North Carolina
city: Akron
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state: Ohio
city: Cincinnati
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city: Columbus
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city: Toledo
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city: Philadelphia
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state: Pennsylvania
city: Philadelphia
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city: Charleston
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state: South Carolina
city: Memphis
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state: Tennessee
city: Dallas
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state: Texas
city: Dallas
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city: Dallas
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city: El Paso
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city: Houston
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state: Utah
city: Richmond
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state: Virginia
city: Seattle
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city: Madison
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state: Wisconsin
city: Buenos Aires
country: Argentina
city: Capital Federal
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Ciudad Autonoma de Buenos Aires
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city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Cordoba
country: Argentina
city: Guaymallen
country: Argentina
city: La Plata, Buenos Aires
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city: Lanus Oeste, Buenos Aires
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city: Rosario
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city: Salta
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city: Tucuman
country: Argentina
city: Woodville
country: Australia
state: South Australia
city: Fitzroy
country: Australia
state: Victoria
city: Heidelberg
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Ottignies
country: Belgium
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: Toronto
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city: Greenfield Park
country: Canada
state: Quebec
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Valdivia
country: Chile
city: Beijing
country: China
city: Chengdu
country: China
city: Chongqing
country: China
city: Shanghai
country: China
city: Olomouc
country: Czech Republic
city: Praha 4
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Kuopio
country: Finland
city: Tampere
country: Finland
city: Bethune
country: France
city: Bron
country: France
city: Montpellier
country: France
city: Rennes
country: France
city: Toulouse
country: France
city: Berlin
country: Germany
city: Bernau
country: Germany
city: Bielefeld
country: Germany
city: Bonn
country: Germany
city: Dusseldorf
country: Germany
city: Erlangen
country: Germany
city: Gottingen
country: Germany
city: Kehl-Kork
country: Germany
city: Mainz
country: Germany
city: Marburg
country: Germany
city: Munchen
country: Germany
city: Ulm
country: Germany
city: Westerstede
country: Germany
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Hong Kong
country: Hong Kong
city: Kowloon
country: Hong Kong
city: Pokfulam
country: Hong Kong
city: Shatin
country: Hong Kong
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Kecskemet
country: Hungary
city: Hyderabad
country: India
city: Hyderabad
country: India
city: Jaipur
country: India
city: Mangalore
country: India
city: Mumbai
country: India
city: Nagpur
country: India
city: Nasik
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Pune
country: India
city: Visakhapatnam
country: India
city: Ashkelon
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Kfar Saba
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Firenze
country: Italy
city: Genova
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Pusan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
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city: Seoul
country: Korea, Republic of
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Valmiera
country: Latvia
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Kuala Lumpur
country: Malaysia
city: Kuala Terengganu
country: Malaysia
city: Aguascalientes
country: Mexico
city: Mexico City, Distrito Federal
country: Mexico
city: Monterrey, Nuevo Leon
country: Mexico
city: San Luis Potosi
country: Mexico
city: Heeze
country: Netherlands
city: Zwolle
country: Netherlands
city: Ermita
country: Philippines
city: Makati City
country: Philippines
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Kazan
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Omsk
country: Russian Federation
city: Samara
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Belgrade
country: Serbia
city: Nis
country: Serbia
city: Novi Sad
country: Serbia
city: Johannesburg
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Cape
city: Cape Town
country: South Africa
city: Granada
country: Spain
state: Andalucia
city: Badalona
country: Spain
state: Cataluna
city: Barcelona
country: Spain
state: Cataluna
city: Barcelona
country: Spain
state: Cataluna
city: Valencia
country: Spain
state: Comunidad Valenciana
city: Alcorcon
country: Spain
state: Madrid, Communidad de
city: Madrid
country: Spain
state: Madrid, Communidad de
city: Baracaldo
country: Spain
state: Pais Vasco
city: Goteborg
country: Sweden
city: Linkoping
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taoyuan
country: Taiwan
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiangmai
country: Thailand
city: Muang
country: Thailand
city: Donetsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Middlesbrough
country: United Kingdom
city: Stoke-on-Trent
country: United Kingdom
Study officials:
affiliation: Eisai Limited
name: Michelle Gee, PhD.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.