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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00700310
First received: June 17, 2008
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Refractory Partial Seizures
Drug: perampanel
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Percent Change in the 28-day Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases) [ Time Frame: Baseline (Pre-randomization) through Week 19 ] [ Designated as safety issue: No ]
    Seizure frequency per 28 days was derived from the information recorded in the subject diaries.


Secondary Outcome Measures:
  • Responder Rate [ Time Frame: Baseline (Pre-randomization) through Week 19 ] [ Designated as safety issue: No ]
    The responder rate for the Full ITT Analysis Set from the maintenance LOCF (Last Observation Carried Forward). A responder was a subject who had a 50 percent or greater reduction in seizure frequency per 28 days from the Pre‑randomization phase.

  • 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) [ Time Frame: Baseline (Pre-randomization) through Week 19 ] [ Designated as safety issue: No ]
    Percent Change in the Seizure frequency per 28 days was derived from the information recorded in the subject diaries.


Enrollment: 712
Study Start Date: September 2008
Study Completion Date: July 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: perampanel
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.
Other Name: E2007
Active Comparator: 2 Drug: perampanel
4 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.
Other Name: E2007
Active Comparator: 3 Drug: perampanel
8 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.
Other Name: E2007
Placebo Comparator: 4 Drug: Placebo
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

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.).
  2. 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;
  3. 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.
  4. 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.);
  5. 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);
  6. Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years that ruled out a progressive cause of epilepsy;
  7. Have uncontrolled partial seizures despite having been treated with at least 2 different anti-epileptic drugs (AEDs) within approximately the last 2 years;
  8. During the 6-week Pre-randomization Phase subjects must have had >/= 5 partial seizures per 6-week (with >/=2 partial seizures per each of 3-week period) and with no 25-day seizure-free period in the 6-week period, as documented via a valid seizure diary. Only simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with secondary generalization are counted toward this inclusion;
  9. 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;
  10. 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;
  11. If on a stable dose (other than intermittent rescue use) of benzodiazepines for epilepsy (or for anxiety or sleep disorders) the prescribed dose must be stable for 1 month (or no less than 21 days) prior to Visit 1. (Note: the use of intermittent rescue benzodiazepines is defined in the exclusion criterion #22 below.) When used in these cases (epilepsy, anxiety or sleep disorders), benzodiazepines will be counted as 1 AED; therefore, only 1 or a maximum of 2 additional approved AEDs will be allowed;
  12. 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.

Exclusion Criteria:

  1. 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;
  2. Pregnant and/or lactating;
  3. Participated in previous perampanel studies;
  4. Presence of nonmotor simple partial seizures only;
  5. Presence of primary generalized epilepsies or seizures, such as absences and or myoclonic epilepsies;
  6. Presence or previous history of Lennox-Gastaut syndrome;
  7. A history of status epilepticus within approximately 12 months prior to Visit 1;
  8. Seizure clusters where individual seizures cannot be counted;
  9. A history of psychogenic seizures;
  10. 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;
  11. 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;
  12. 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);
  13. 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);
  14. A clinically significant ECG abnormality, including prolonged QTc defined as >450 msec;
  15. 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.
  16. Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors;
  17. History of drug or alcohol dependency or abuse within approximately the last 2 years;
  18. Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions;
  19. If felbamate is used as a concomitant AED, subjects must be on felbamate for at least 2 years, with a stable dose for 2 months (or no less than 49 days) prior to Visit 1. They must not have a history of white blood cell (WBC) count below 2500/µL (2.50 1E+09/L), platelets below 100,000, liver function tests (LFTs) above 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate. If patients received felbamate in the past, it must have been discontinued 2 months (or no less than 49 days) prior to Visit 1;
  20. Concomitant use of vigabatrin. Subjects who took vigabatrin in the past must be off vigabatrin for approximately 5 months prior to Visit 1 and must have documentation showing no evidence of a vigabatrin associated clinically significant abnormality in a visual perimetry test;
  21. Concomitant use of barbiturates (except for seizure control indication) within 1 month (or no less than 21 days) prior to Visit 1;
  22. Use of intermittent rescue benzodiazepines (ie, 1-2 doses over a 24-hr period considered one-time rescue) 2 or more times in a 1-month period prior to Visit 1; or
  23. Any condition(s) that will make the subject, in the opinion of the Investigator, unsuitable for the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00700310

  Hide Study Locations
Locations
Australia, South Australia
The Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Clayton, Victoria, Australia, 3168
Fitzroy, Victoria, Australia, 3065
Heidelberg, Victoria, Australia, 3081
Parkville, Victoria, Australia, 3050
Australia
Clayton, Australia, 3168
Fitzroy, Australia, 3065
Parkville, Australia, 3050
West Heidelberg, Australia, 3081
Woodville, Australia, 5011
Bulgaria
Pleven, Bulgaria, 5800
Plovdiv, Bulgaria, 4002
Sofia, Bulgaria, 1606
Sofia, Bulgaria, 1113
Czech Republic
Brno, Czech Republic, 625 00
Olomouc, Czech Republic, 775 20
Praha 4, Czech Republic, 140 59
Praha 5, Czech Republic, 150 06
Estonia
Tallinn, Estonia, EE-13419
Tallinn, Estonia, EE-10617
Tartu, Estonia, EE-51014
Germany
Dusseldorf, Germany, 40212
Kehl-Kork, Germany, 77694
Konigstein-Falkenstein, Germany, D-61462
Mainz, Germany, 55101
Marburg, Germany, 35039
Munchen, Germany, 80333
Munchen, Germany, 81377
Ulm, Germany, 89075
Westerstede, Germany, 26655
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong, 999077
Hong Kong, Hong Kong
Queen Elizabeth Hospital
Kowloon, Hong Kong
United Christian Hospital
Kowloon, Hong Kong
Kowloon, Hong Kong
Prince of Wales Hospital
Shatin, Hong Kong
Hungary
Budapest, Hungary, 1145
Budapest, Hungary, 1146
Budapest, Hungary, 1096
Budapest, Hungary, 1083
Kecskemet, Hungary, 6000
India
Hyderabad, Andhra Pradesh, India, 500082
Hyderabad, Andhra Pradesh, India, 500001
Vishakhapatnam, Andhra Pradesh, India, 530002
Mumbai, Maharashtra, India, 400026
Pune, Maharashtra, India, 411030
Pune, Maharashtra, India, 411011
Jaipur, Rajasthan, India, 302004
New Delhi, India, 110002
Italy
Milano, Italy, 20133
Napoli, Italy, 80128
Padova, Italy, 35128
Siena, Italy, 53100
Torino, Italy, 10126
Korea, Republic of
Busan, Korea, Republic of, 614735
Busan, Korea, Republic of, 602715
Daegu, Korea, Republic of, 700712
Seoul, Korea, Republic of, 138736
Seoul, Korea, Republic of, 120752
Seoul, Korea, Republic of, 135710
Seoul, Korea, Republic of, 110744
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 Terengganu, Terengganu, Malaysia, 24000
Kuala Lumpur, Wilayah Persekutuan, Malaysia, 59100
Philippines
Ermita, Philippines, 1000
Makati City, Philippines, 1229
Poland
Bialystok, Poland, 15-276
Gdansk, Poland, 80-803
Gdansk, Poland, 80-952
Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
Katowice, Poland, 40-635
Katowice, Poland, 40-635
Lodz, Poland, 93-513
Lublin, Poland, 20-718
Warszawa, Poland, 02-957
Portugal
Coimbra, Portugal, 3000-075
Lisboa, Portugal, 1649-035
Porto, Portugal, 4099-001
Porto, Portugal, 4200-319
Romania
Brasov, Romania, 500061
Colentina Clinical Hospital
Bucharest, Romania, 020125
Sapiens Medical Center
Bucharest, Romania, 011635
Bucharest, Romania, 011635
Bucharest, Romania, 20125
Cluj Napoca, Romania, 400012
Pediatric Neurology Clinic of Emergency Children Hospital
Cluj Napoca, Romania, 400012
Emergency County Clinical Hospital
Cluj Napoca, Romania, 400012
Russian Federation
Ekaterinburg, Russian Federation, 620149
Moscow Research Institute of Pediatrics and Pediatric Surgery
Moscow, Russian Federation, 125412
Moscow Research Institute of Psychiatry
Moscow, Russian Federation, 107076
Moscow State University of Medicine and Dentistry
Moscow, Russian Federation, 107066
Moscow, Russian Federation, 107076
Moscow, Russian Federation, 107066
Moscow, Russian Federation, 125412
Samara, Russian Federation, 443095
Tyumen, Russian Federation, 625039
Yaroslavl, Russian Federation, 150030
Serbia
Belgrade, Serbia, 11000
Nis, Serbia, 18000
Novi Sad, Serbia, 21000
Spain
Granada, Andalucia, Spain, 18012
Badalona, Cataluna, Spain, 8916
Barcelona, Cataluna, Spain, 8025
Barcelona, Cataluna, Spain, 8003
Alcorcon, Comunidad de Madrid, Spain, 28922
Madrid, Comunidad de Madrid, Spain, 28040
Valencia, Comunidad Valenciana, Spain, 46014
Valencia, Comunidad Valenciana, Spain, 46009
Barcelona, Spain, 08003
Valencia, Spain, 46009
Taiwan
Kaohsiung, Taiwan, 833
Taichung, Taiwan, 404
Taichung, Taiwan, 40705
Tainan, Taiwan, 704
Taoyuan, Taiwan, 333
Thailand
Bangkok, Thailand, 10330
Bangkok, Thailand, 10700
Bangkok, Thailand, 10400
Chiang Mai, Thailand, 50200
Khon Kaen, Thailand, 40004
Muang District, Thailand, 34000
Ukraine
Dnipropetrovsk, Ukraine, 49027
Dnipropetrovsk, Ukraine, 40927
Donetsk, Ukraine, 83114
Donetsk, Ukraine, 83052
Kharkiv, Ukraine, 61068
Kharkiv, Ukraine, 61018
Kyiv, Ukraine, 04080
Kyiv, Ukraine, 04209
Kyiv, Ukraine, 040209
Lviv, Ukraine, 79010
Uzhgorod, Ukraine, 88018
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: David Squillacote, M.D. Eisai Inc.
  More Information

No publications provided by Eisai Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00700310     History of Changes
Other Study ID Numbers: E2007-G000-306
Study First Received: June 17, 2008
Results First Received: October 23, 2012
Last Updated: October 23, 2012
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Partial onset seizures
E2007
perampanel
refractory partial seizures
adjunctive therapy
seizure frequency
reduction in seizure frequency
safety
concomitant AED(s)

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on April 14, 2014