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Refractory Partial SeizuresPhase 3NCT00700310

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

A Phase 3 study testing perampanel in people with Refractory Partial Seizures, run by Eisai Inc. at 137 sites in 23 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 to 120 years
Conditions the study is for
Refractory Partial Seizures
What is being tested?
perampanel
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
712 participants
Where
137 sitesin 23 countries
Study dates
Aug 2008to Jan 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 120 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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;
Show all 12Show fewer
  • Have uncontrolled partial seizures despite having been treated with at least 2 different anti-epileptic drugs (AEDs) within approximately the last 2 years;
  • 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;
  • 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;
  • 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;
  • 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.

Who cannot join

  • 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;
Show all 23Show fewer
  • 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.
  • Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors;
  • History of drug or alcohol dependency or abuse within approximately the last 2 years;
  • 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;
  • 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;
  • 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;
  • Concomitant use of barbiturates (except for seizure control indication) within 1 month (or no less than 21 days) prior to Visit 1;
  • 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
  • Any condition(s) that will make the subject, in the opinion of the Investigator, unsuitable for the study.

Trial locations and contacts

137 sites in 23 countries.

137 sites in 23 countries

Australia11 sites

  • Study site

    Clayton, Victoria, 3168

  • Study site

    Clayton, 3168

  • Study site

    Fitzroy, Victoria, 3065

  • Study site

    Fitzroy, 3065

  • Study site

    Heidelberg, Victoria, 3081

  • Study site

    Parkville, Victoria, 3050

  • Study site

    Parkville, 3050

  • Study site

    West Heidelberg, 3081

  • The Queen Elizabeth Hospital

    Woodville, South Australia, 5011

  • Study site

    Woodville, 5011

  • Study site

    Woodville South, South Australia, 5011

Other trials in Australia

Ukraine11 sites

  • Study site

    Dnipropetrovsk, 40927

  • Study site

    Dnipropetrovsk, 49027

  • Study site

    Donetsk, 83052

  • Study site

    Donetsk, 83114

  • Study site

    Kharkiv, 61018

  • Study site

    Kharkiv, 61068

  • Study site

    Kyiv, 040209

  • Study site

    Kyiv, 04080

  • Study site

    Kyiv, 04209

  • Study site

    Lviv, 79010

  • Study site

    Uzhhorod, 88018

Other trials in Ukraine

Russia10 sites

  • Moscow State University of Medicine and Dentistry

    Moscow, 107066

  • Study site

    Moscow, 107066

  • Moscow Research Institute of Psychiatry

    Moscow, 107076

  • Study site

    Moscow, 107076

  • Moscow Research Institute of Pediatrics and Pediatric Surgery

    Moscow, 125412

  • Study site

    Moscow, 125412

  • Study site

    Samara, 443095

  • Study site

    Tyumen, 625039

  • Study site

    Yaroslavl, 150030

  • Study site

    Yekaterinburg, 620149

Other trials in Russia

Spain10 sites

  • Study site

    Alcorcón, Madrid, 28922

  • Study site

    Badalona, Catalonia, 8916

  • Study site

    Barcelona, Catalonia, 8003

  • Study site

    Barcelona, Catalonia, 8025

  • Study site

    Barcelona, 08003

  • Study site

    Granada, Andalusia, 18012

  • Study site

    Madrid, Madrid, 28040

  • Study site

    Valencia, Valencia, 46009

  • Study site

    Valencia, Valencia, 46014

  • Study site

    Valencia, 46009

Other trials in Spain

Germany9 sites

  • Study site

    Düsseldorf, 40212

  • Study site

    Kehl-Kork, 77694

  • Study site

    Konigstein-Falkenstein, D-61462

  • Study site

    Mainz, 55101

  • Study site

    Marburg, 35039

  • Study site

    München, 80333

  • Study site

    München, 81377

  • Study site

    Ulm, 89075

  • Study site

    Westerstede, 26655

Other trials in Germany

India8 sites

  • Study site

    Hyderabad, Andhra Pradesh, 500001

  • Study site

    Hyderabad, Andhra Pradesh, 500082

  • Study site

    Jaipur, Rajasthan, 302004

  • Study site

    Mumbai, Maharashtra, 400026

  • Study site

    New Delhi, 110002

  • Study site

    Pune, Maharashtra, 411011

  • Study site

    Pune, Maharashtra, 411030

  • Study site

    Visakhapatnam, Andhra Pradesh, 530002

Other trials in India

Poland8 sites

  • Study site

    Bialystok, 15-276

  • Study site

    Gdansk, 80-803

  • Study site

    Gdansk, 80-952

  • Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

    Katowice, 40-635

  • Study site

    Katowice, 40-635

  • Study site

    Lodz, 93-513

  • Study site

    Lublin, 20-718

  • Study site

    Warsaw, 02-957

Other trials in Poland

Romania8 sites

  • Study site

    Brasov, 500061

  • Sapiens Medical Center

    Bucharest, 011635

  • Study site

    Bucharest, 011635

  • Colentina Clinical Hospital

    Bucharest, 020125

  • Study site

    Bucharest, 20125

  • Emergency County Clinical Hospital

    Cluj-Napoca, 400012

  • Pediatric Neurology Clinic of Emergency Children Hospital

    Cluj-Napoca, 400012

  • Study site

    Cluj-Napoca, 400012

Other trials in Romania

South Korea7 sites

  • Study site

    Busan, 602715

  • Study site

    Busan, 614735

  • Study site

    Daegu, 700712

  • Study site

    Seoul, 110744

  • Study site

    Seoul, 120752

  • Study site

    Seoul, 135710

  • Study site

    Seoul, 138736

Other trials in South Korea

Hong Kong6 sites

  • Queen Mary Hospital

    Hong Kong, 999077

  • Study site

    Hong Kong

  • Queen Elizabeth Hospital

    Kowloon

  • United Christian Hospital

    Kowloon

  • Study site

    Kowloon

  • Prince of Wales Hospital

    Shatin

Other trials in Hong Kong

Thailand6 sites

  • Study site

    Bangkok, 10330

  • Study site

    Bangkok, 10400

  • Study site

    Bangkok, 10700

  • Study site

    Chiang Mai, 50200

  • Study site

    Khon Kaen, 40004

  • Study site

    Muang District, 34000

Other trials in Thailand

Hungary5 sites

  • Study site

    Budapest, 1083

  • Study site

    Budapest, 1096

  • Study site

    Budapest, 1145

  • Study site

    Budapest, 1146

  • Study site

    Kecskemét, 6000

Other trials in Hungary

Italy5 sites

  • Study site

    Milan, 20133

  • Study site

    Naples, 80128

  • Study site

    Padova, 35128

  • Study site

    Siena, 53100

  • Study site

    Torino, 10126

Other trials in Italy

Taiwan5 sites

  • Study site

    Kaohsiung City, 833

  • Study site

    Taichung, 404

  • Study site

    Taichung, 40705

  • Study site

    Tainan, 704

  • Study site

    Taoyuan, 333

Other trials in Taiwan

Bulgaria4 sites

  • Study site

    Pleven, 5800

  • Study site

    Plovdiv, 4002

  • Study site

    Sofia, 1113

  • Study site

    Sofia, 1606

Other trials in Bulgaria

Czechia4 sites

  • Study site

    Brno, 625 00

  • Study site

    Olomouc, 775 20

  • Study site

    Prague, 140 59

  • Study site

    Prague, 150 06

Other trials in Czechia

Portugal4 sites

  • Study site

    Coimbra, 3000-075

  • Study site

    Lisbon, 1649-035

  • Study site

    Porto, 4099-001

  • Study site

    Porto, 4200-319

Other trials in Portugal

Estonia3 sites

  • Study site

    Tallinn, EE-10617

  • Study site

    Tallinn, EE-13419

  • Study site

    Tartu, EE-51014

Other trials in Estonia

Latvia3 sites

  • Study site

    Riga, LV-1004

  • Study site

    Riga, LV-1038

  • Study site

    Valmiera, LV-4201

Other trials in Latvia

Lithuania3 sites

  • Study site

    Kaunas, LT-50009

  • Study site

    Klaipėda, LT-92288

  • Study site

    Vilnius, LT-08661

Other trials in Lithuania

Serbia3 sites

  • Study site

    Belgrade, 11000

  • Study site

    Niš, 18000

  • Study site

    Novi Sad, 21000

Other trials in Serbia

Malaysia2 sites

  • Study site

    Kuala Lumpur, Kuala Lumpur, 59100

  • Study site

    Kuala Terengganu, Terengganu, 24000

Other trials in Malaysia

Philippines2 sites

  • Study site

    Ermita, 1000

  • Study site

    Makati City, 1229

Other trials in Philippines

About this study

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

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.

Being tested
perampanel, Placebo
Keywords
Partial onset seizures, E2007, perampanel, refractory partial seizures, adjunctive therapy, seizure frequency, reduction in seizure frequency, safety, concomitant AED(s)
Medical subject headings
Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • perampanelDrug

    Also called E2007

    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.

  • perampanelDrug

    Also called E2007

    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.

  • perampanelDrug

    Also called E2007

    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.

  • PlaceboDrug

    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.

Study groups in NCT00700310
Study groupRoleWhat they receive
1Active comparatorNot described
Receives: Drug: perampanel
2Active comparatorNot described
Receives: Drug: perampanel
3Active comparatorNot described
Receives: Drug: perampanel
4Placebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (Pre-randomization) through Week 19

Secondary outcomes (2)

  1. Responder Rate

    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.

    Measured: Baseline (Pre-randomization) through Week 19

  2. 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)

    Percent Change in the Seizure frequency per 28 days was derived from the information recorded in the subject diaries.

    Measured: Baseline (Pre-randomization) through Week 19

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionAug 2009
  4. Study completionJan 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
712 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00700310
Sponsor's protocol ID
E2007-G000-306
Other IDs
2007-006169-33
Status last verified
Nov 2015
First submitted
17 Jun 2008
Last updated
21 Jan 2016

Publications

  • 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.

    PubMed 37059702

  • 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.

    PubMed 35305920

  • 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.

    PubMed 25878175

  • 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.

    PubMed 25823975

  • 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.

    PubMed 23663001

  • 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.

    PubMed 22517103

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing perampanel in people with Refractory Partial Seizures, run by Eisai Inc. at 137 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 137 sites in Australia, Ukraine, Russia, Spain, Germany and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00700310, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2016.

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