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

NCT ID: NCT00700310

Last Updated: 2016-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 712 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2010-01-31

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.

Conditions

Refractory Partial Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

perampanel

Intervention Type: DRUG

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.

2

Group Type: ACTIVE_COMPARATOR

perampanel

Intervention Type: DRUG

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.

3

Group Type: ACTIVE_COMPARATOR

perampanel

Intervention Type: DRUG

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.

4

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

E2007; E2007; E2007

Eligibility 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Squillacote, M.D.

Role: STUDY_DIRECTOR

Eisai Inc.

Locations

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Woodville South, South Australia, Australia

Clayton, Victoria, Australia

Fitzroy, Victoria, Australia

Heidelberg, Victoria, Australia

Parkville, Victoria, Australia

Clayton, , Australia

Fitzroy, , Australia

Parkville, , Australia

West Heidelberg, , Australia

Woodville, , Australia

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Sofia, , Bulgaria

Brno, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Prague, , Czechia

Tallinn, , Estonia

Tallinn, , Estonia

Tartu, , Estonia

Düsseldorf, , Germany

Kehl-Kork, , Germany

Konigstein-Falkenstein, , Germany

Mainz, , Germany

Marburg, , Germany

München, , Germany

München, , Germany

Ulm, , Germany

Westerstede, , Germany

Queen Mary Hospital

Hong Kong, , Hong Kong

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

Budapest, , Hungary

Budapest, , Hungary

Budapest, , Hungary

Budapest, , Hungary

Kecskemét, , Hungary

Hyderabad, Andhra Pradesh, India

Hyderabad, Andhra Pradesh, India

Visakhapatnam, Andhra Pradesh, India

Mumbai, Maharashtra, India

Pune, Maharashtra, India

Pune, Maharashtra, India

Jaipur, Rajasthan, India

New Delhi, , India

Milan, , Italy

Napoli, , Italy

Padua, , Italy

Siena, , Italy

Torino, , Italy

Riga, , Latvia

Riga, , Latvia

Valmiera, , Latvia

Kaunas, , Lithuania

Klaipėda, , Lithuania

Vilnius, , Lithuania

Kuala Lumpur, Kuala Lumpur, Malaysia

Kuala Terengganu, Terengganu, Malaysia

Ermita, , Philippines

Makati City, , Philippines

Bialystok, , Poland

Gdansk, , Poland

Gdansk, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, , Poland

Katowice, , Poland

Lodz, , Poland

Lublin, , Poland

Warsaw, , Poland

Coimbra, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Porto, , Portugal

Brasov, , Romania

Sapiens Medical Center

Bucharest, , Romania

Bucharest, , Romania

Colentina Clinical Hospital

Bucharest, , Romania

Bucharest, , Romania

Emergency County Clinical Hospital

Cluj-Napoca, , Romania

Pediatric Neurology Clinic of Emergency Children Hospital

Cluj-Napoca, , Romania

Cluj-Napoca, , Romania

Moscow State University of Medicine and Dentistry

Moscow, , Russia

Moscow, , Russia

Moscow Research Institute of Psychiatry

Moscow, , Russia

Moscow, , Russia

Moscow Research Institute of Pediatrics and Pediatric Surgery

Moscow, , Russia

Moscow, , Russia

Samara, , Russia

Tyumen, , Russia

Yaroslavl, , Russia

Yekaterinburg, , Russia

Belgrade, , Serbia

Niš, , Serbia

Novi Sad, , Serbia

Busan, , South Korea

Busan, , South Korea

Daegu, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Granada, Andalusia, Spain

Badalona, Catalonia, Spain

Barcelona, Catalonia, Spain

Barcelona, Catalonia, Spain

Alcorcón, Madrid, Spain

Madrid, Madrid, Spain

Valencia, Valencia, Spain

Valencia, Valencia, Spain

Barcelona, , Spain

Valencia, , Spain

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Taoyuan District, , Taiwan

Bangkok, , Thailand

Bangkok, , Thailand

Bangkok, , Thailand

Chiang Mai, , Thailand

Khon Kaen, , Thailand

Muang District, , Thailand

Dnipropetrovsk, , Ukraine

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Donetsk, , Ukraine

Kharkiv, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Kyiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Uzhhorod, , Ukraine

Countries

Australia; Bulgaria; Czechia; Estonia; Germany; Hong Kong; Hungary; India; Italy; Latvia; Lithuania; Malaysia; Philippines; Poland; Portugal; Romania; Russia; Serbia; South Korea; Spain; Taiwan; Thailand; Ukraine

References

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.

Reference Type: DERIVED

PMID: 37059702 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35305920 (View on PubMed)

French 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.

Reference Type: DERIVED

PMID: 25878175 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25823975 (View on PubMed)

Steinhoff 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.

Reference Type: DERIVED

PMID: 23663001 (View on PubMed)

Krauss 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.

Reference Type: DERIVED

PMID: 22517103 (View on PubMed)

Other Identifiers

2007-006169-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2007-G000-306

Identifier Type: -

Identifier Source: org_study_id