Evaluating Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures
A Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Study to Evaluate the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures
2 other identifiers
interventional
712
22 countries
134
Brief Summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of perampanel when given as an adjunctive therapy in subjects with refractory partial seizures.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2008
134 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 17, 2008
CompletedFirst Posted
Study publicly available on registry
June 18, 2008
CompletedStudy Start
First participant enrolled
August 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2010
CompletedResults Posted
Study results publicly available
November 22, 2012
CompletedJanuary 21, 2016
November 1, 2015
1 year
June 17, 2008
October 23, 2012
December 17, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percent Change in the 28-day Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases)
Seizure frequency per 28 days was derived from the information recorded in the subject diaries.
Baseline (Pre-randomization) through Week 19
Secondary Outcomes (2)
Responder Rate
Baseline (Pre-randomization) through Week 19
Percent Change in the 28-day Complex Partial Plus Secondarily Generalized Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases)
Baseline (Pre-randomization) through Week 19
Study Arms (4)
1
ACTIVE COMPARATOR2
ACTIVE COMPARATOR3
ACTIVE COMPARATOR4
PLACEBO COMPARATORInterventions
2 mg perampanel or placebo in a 1:1:1:1 ratio, 170 subjects/arm, a total of 680 subjects. All subjects will take a maximum of 6 tablets daily and will be up-titrated weekly in 2-mg increments to their randomized dose.
Placebo in a 1:1:1:1 ratio, 170 subjects/arm, a total of 680 subjects. All subjects will take a maximum of 6 tablets daily.
Eligibility Criteria
You may qualify if:
- Provide written informed consent signed by the subject or legal guardian prior to entering the study or undergoing any study procedures (If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained.).
- Be considered reliable and willing to be available for the study period and able to record seizures and report AEs them self or have a caregiver who can record seizures and report AEs for them;
- Male or female and greater than or equal to 12 years of age (within the course of the study), or greater than or equal to 18 years of age (depending on location) at the time of signing the informed consent.
- Females should be 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 must have a negative serum beta-human chorionic gonadotropin (ß-hCG) at Visit 1 and a negative urine pregnancy test prior to randomization at Visit 2. Female subjects of childbearing potential must agree to be abstinent or to use at least 1 medically acceptable methods of contraception (eg, a double-barrier method \[eg, condom + spermicide, condom + diaphragm with spermicide\], IUD, or have a vasectomised partner) starting at Visit 1 and throughout the entire study period and for 2 months after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously) starting at Visit 1 and continuing throughout the entire study period and for 2 months after the last dose of study drug. (It is not required for male subjects to use contraceptive measures based on preclinical toxicology data.);
- Have a diagnosis of epilepsy with partial seizures with or without secondarily generalized seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and an electroencephalogram (EEG) that is consistent with localization-related epilepsy; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history);
- Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years that ruled out a progressive cause of epilepsy;
- Have uncontrolled partial seizures despite having been treated with at least 2 different anti-epileptic drugs (AEDs) within approximately the last 2 years;
- Are currently being treated with stable doses of 1, 2 or a maximum of 3 approved AEDs. Only 1 inducer AED (defined as; carbamazepine, phenytoin, phenobarbital, or primidone only) out of the maximum of 3 AEDs is allowed;
- Are on a stable dose of the same concomitant AED(s) for 1 month (or no less than 21 days) prior to Visit 1; in the case where a new AED regime has been initiated for a subject, the dose must be stable for 2 months (or no less than 49 days) prior to Visit 1;
- A vagal nerve stimulator (VNS) is allowed but it must have been implanted \>/= 5 months prior to Visit 1. Stimulator parameters can not be changed for 1 month (or no less than 21 days) prior to Visit 1 or thereafter during the study.
You may not qualify if:
- Participated in a study involving administration of an investigational compound or device within 1 month (or no less than 21 days) prior to Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer;
- Pregnant and/or lactating;
- Participated in previous perampanel studies;
- Presence of nonmotor simple partial seizures only;
- Presence of primary generalized epilepsies or seizures, such as absences and or myoclonic epilepsies;
- Presence or previous history of Lennox-Gastaut syndrome;
- A history of status epilepticus within approximately 12 months prior to Visit 1;
- Seizure clusters where individual seizures cannot be counted;
- A history of psychogenic seizures;
- Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the Investigator(s) could affect the subject's safety or the study conduct;
- Scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1; however those who have previously documented "failed" epilepsy surgery will be allowed;
- Evidence of significant active hepatic disease. Stable elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) due to concomitant medication(s) will be allowed if they are less than 3 times the upper limit of normal (ULN);
- Evidence of significant active hematological disease; white blood cell (WBC) count \<= 2500/µL (2.50 1E+09/L) or an absolute neutrophil count \<= 1000/µL (1.00 1E+09/L);
- A clinically significant ECG abnormality, including prolonged QTc defined as \>450 msec;
- Suffering from psychotic disorder(s) and/or unstable recurrent affective disorder(s) evident by use of antipsychotics or have had a suicide attempt(s) within the last 2 years.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
Study Sites (137)
The Queen Elizabeth Hospital
Woodville, South Australia, 5011, Australia
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Woodville South, South Australia, 5011, Australia
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Clayton, Victoria, 3168, Australia
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Fitzroy, Victoria, 3065, Australia
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Heidelberg, Victoria, 3081, Australia
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Parkville, Victoria, 3050, Australia
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Clayton, 3168, Australia
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Fitzroy, 3065, Australia
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Parkville, 3050, Australia
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West Heidelberg, 3081, Australia
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Woodville, 5011, Australia
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Pleven, 5800, Bulgaria
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Plovdiv, 4002, Bulgaria
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Sofia, 1113, Bulgaria
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Sofia, 1606, Bulgaria
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Brno, 625 00, Czechia
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Olomouc, 775 20, Czechia
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Prague, 140 59, Czechia
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Prague, 150 06, Czechia
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Tallinn, EE-10617, Estonia
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Tallinn, EE-13419, Estonia
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Tartu, EE-51014, Estonia
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Düsseldorf, 40212, Germany
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Kehl-Kork, 77694, Germany
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Konigstein-Falkenstein, D-61462, Germany
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Mainz, 55101, Germany
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Marburg, 35039, Germany
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München, 80333, Germany
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München, 81377, Germany
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Ulm, 89075, Germany
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Westerstede, 26655, Germany
Queen Mary Hospital
Hong Kong, 999077, Hong Kong
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Hong Kong, Hong Kong
Queen Elizabeth Hospital
Kowloon, Hong Kong
United Christian Hospital
Kowloon, Hong Kong
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Kowloon, Hong Kong
Prince of Wales Hospital
Shatin, Hong Kong
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Budapest, 1083, Hungary
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Budapest, 1096, Hungary
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Budapest, 1145, Hungary
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Budapest, 1146, Hungary
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Kecskemét, 6000, Hungary
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Hyderabad, Andhra Pradesh, 500001, India
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Hyderabad, Andhra Pradesh, 500082, India
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Visakhapatnam, Andhra Pradesh, 530002, India
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Mumbai, Maharashtra, 400026, India
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Pune, Maharashtra, 411011, India
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Pune, Maharashtra, 411030, India
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Jaipur, Rajasthan, 302004, India
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New Delhi, 110002, India
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Milan, 20133, Italy
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Napoli, 80128, Italy
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Padua, 35128, Italy
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Siena, 53100, Italy
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Torino, 10126, Italy
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Riga, LV-1004, Latvia
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Riga, LV-1038, Latvia
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Valmiera, LV-4201, Latvia
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Kaunas, LT-50009, Lithuania
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Klaipėda, LT-92288, Lithuania
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Vilnius, LT-08661, Lithuania
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Kuala Lumpur, Kuala Lumpur, 59100, Malaysia
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Kuala Terengganu, Terengganu, 24000, Malaysia
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Ermita, 1000, Philippines
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Makati City, 1229, Philippines
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Bialystok, 15-276, Poland
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Gdansk, 80-803, Poland
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Gdansk, 80-952, Poland
Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
Katowice, 40-635, Poland
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Katowice, 40-635, Poland
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Lodz, 93-513, Poland
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Lublin, 20-718, Poland
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Warsaw, 02-957, Poland
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Coimbra, 3000-075, Portugal
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Lisbon, 1649-035, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200-319, Portugal
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Brasov, 500061, Romania
Sapiens Medical Center
Bucharest, 011635, Romania
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Bucharest, 011635, Romania
Colentina Clinical Hospital
Bucharest, 020125, Romania
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Bucharest, 20125, Romania
Emergency County Clinical Hospital
Cluj-Napoca, 400012, Romania
Pediatric Neurology Clinic of Emergency Children Hospital
Cluj-Napoca, 400012, Romania
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Cluj-Napoca, 400012, Romania
Moscow State University of Medicine and Dentistry
Moscow, 107066, Russia
Unknown Facility
Moscow, 107066, Russia
Moscow Research Institute of Psychiatry
Moscow, 107076, Russia
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Moscow, 107076, Russia
Moscow Research Institute of Pediatrics and Pediatric Surgery
Moscow, 125412, Russia
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Moscow, 125412, Russia
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Samara, 443095, Russia
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Tyumen, 625039, Russia
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Yaroslavl, 150030, Russia
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Yekaterinburg, 620149, Russia
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Belgrade, 11000, Serbia
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Niš, 18000, Serbia
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Novi Sad, 21000, Serbia
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Busan, 602715, South Korea
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Busan, 614735, South Korea
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Daegu, 700712, South Korea
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Seoul, 110744, South Korea
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Seoul, 120752, South Korea
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Seoul, 135710, South Korea
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Seoul, 138736, South Korea
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Granada, Andalusia, 18012, Spain
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Badalona, Catalonia, 8916, Spain
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Barcelona, Catalonia, 8003, Spain
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Barcelona, Catalonia, 8025, Spain
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Alcorcón, Madrid, 28922, Spain
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Madrid, Madrid, 28040, Spain
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Valencia, Valencia, 46009, Spain
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Valencia, Valencia, 46014, Spain
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Barcelona, 08003, Spain
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Valencia, 46009, Spain
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Kaohsiung City, 833, Taiwan
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Taichung, 404, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10330, Thailand
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Bangkok, 10400, Thailand
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Bangkok, 10700, Thailand
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Chiang Mai, 50200, Thailand
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Khon Kaen, 40004, Thailand
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Muang District, 34000, Thailand
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Dnipropetrovsk, 40927, Ukraine
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Dnipropetrovsk, 49027, Ukraine
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Donetsk, 83052, Ukraine
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Donetsk, 83114, Ukraine
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Kharkiv, 61018, Ukraine
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Kharkiv, 61068, Ukraine
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Kyiv, 040209, Ukraine
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Kyiv, 04080, Ukraine
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Kyiv, 04209, Ukraine
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Lviv, 79010, Ukraine
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Uzhhorod, 88018, Ukraine
Related Publications (6)
Bresnahan R, Hill RA, Wang J. Perampanel add-on for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2023 Apr 14;4(4):CD010961. doi: 10.1002/14651858.CD010961.pub2.
PMID: 37059702DERIVEDMaguire 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.
PMID: 35305920DERIVEDFrench JA, Gil-Nagel A, Malerba S, Kramer L, Kumar D, Bagiella E. Time to prerandomization monthly seizure count in perampanel trials: A novel epilepsy endpoint. Neurology. 2015 May 19;84(20):2014-20. doi: 10.1212/WNL.0000000000001585. Epub 2015 Apr 15.
PMID: 25878175DERIVEDRosenfeld 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.
PMID: 25823975DERIVEDSteinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, Squillacote D, Yang H, Zhu J, Laurenza A. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013 Aug;54(8):1481-9. doi: 10.1111/epi.12212. Epub 2013 May 10.
PMID: 23663001DERIVEDKrauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J, Yang H, Squillacote D, Edwards HB, Zhu J, Laurenza A. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012 May 1;78(18):1408-15. doi: 10.1212/WNL.0b013e318254473a. Epub 2012 Apr 18.
PMID: 22517103DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Eisai Inc.
- Organization
- Eisai Call Center
Study Officials
- STUDY DIRECTOR
David Squillacote, M.D.
Eisai Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 17, 2008
First Posted
June 18, 2008
Study Start
August 1, 2008
Primary Completion
August 1, 2009
Study Completion
January 1, 2010
Last Updated
January 21, 2016
Results First Posted
November 22, 2012
Record last verified: 2015-11