Clinical Trials Register

Summary
EudraCT Number:	2014-002321-35
Sponsor's Protocol Code Number:	E2007-G000-338
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-05-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Latvia - SAM

A.2

EudraCT number

2014-002321-35

A.3

Full title of the trial

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial With an Open-Label Extension Phase of Perampanel as Adjunctive Treatment in Subjects at Least 2 years of Age With Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A global study completed at hospitals in US, Europe & Asia using an investigational drug (Perampanel) to research its safety & effectiveness in patients who are at least 2 years of age with Lennox-Gastaut Syndrome

A.4.1

Sponsor's protocol code number

E2007-G000-338

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02834793

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Eisai Limited
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Eisai Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eisai Europe Ltd.
B.5.2	Functional name of contact point	Medical Information
B.5.3	Address:
B.5.3.1	Street Address	European Knowledge Centre, Mosquito Way
B.5.3.2	Town/ city	Hatfield
B.5.3.3	Post code	AL10 9SN
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	440208600 1400
B.5.5	Fax number	440208600 1388
B.5.6	E-mail	EUMedInfo@eisai.net

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fycompa
D.2.1.1.2	Name of the Marketing Authorisation holder	Eisai Europe Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	perampanel
D.3.2	Product code	E2007
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	perampanel
D.3.9.1	CAS number	380917-97-5
D.3.9.2	Current sponsor code	E2007
D.3.9.3	Other descriptive name	PERAMPANEL
D.3.9.4	EV Substance Code	SUB32160
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fycompa
D.2.1.1.2	Name of the Marketing Authorisation holder	Eisai Europe Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	perampanel
D.3.2	Product code	E2007
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Perampanel
D.3.9.1	CAS number	380917-97-5
D.3.9.2	Current sponsor code	E2007
D.3.9.3	Other descriptive name	PERAMPANEL
D.3.9.4	EV Substance Code	SUB32160
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Seizures associated with Lennox-Gastaut Syndrome (LGS)

E.1.1.1

Medical condition in easily understood language

Epilepsy

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10048816
E.1.2	Term	Lennox-Gastaut syndrome
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to demonstrate that perampanel given as adjunctive antiepileptic treatment is superior compared to placebo in reducing the incidence of drop seizures during 18 weeks of treatment in subjects with inadequately controlled seizures associated with LGS.

E.2.2

Secondary objectives of the trial

1. To demonstrate that peramapanel is superior to placebo in reducing the incidence of all seizures.
2. To demonstrate that perampanel is superior to placebo in the 50%, 75%, 100% responder rates for drop seizures.
3. To demonstrate that perampanel is superior to placebo in the 50%, 75%, 100% responder rates for total seizures.
4. To demonstrate that perampanel is superior to placebo in reducing the incidence of non-drop seizures.
5. To evaluate the 50%, 75%, and 100% responder rates in non-drop seizure frequency.
6. To evaluate physicians’ global evaluation of subjects’ overall changes in symptoms
7. To evaluate the safety of perampanel.
8. To evaluate the PK and PK/PD relationships of perampanel associated with LGS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must meet all of the following criteria to be included in this study:
1. Subjects must have diagnosis of LGS as evidenced by:
a. More than one type of generalized seizures, including drop seizures (atonic, tonic, or myoclonic) for at least 6 months before Visit 1
b. An EEG reporting diagnostic criteria for LGS at some point in their history (abnormal background activity accompanied by slow, spike and wave pattern <2.5 Hz)
2. Subjects must be at least 2 years old at the time of consent.
3. Subjects must have been <11 years old at the onset of LGS.
4. Subjects must have experienced at least 2 drop seizures per week in the 4 -week Baseline Period preceding randomization; the Baseline Period within the Prerandomization Phase is 4 weeks.
5. Subjects must have been receiving 1 to 3 concomitant AEDs at a stable dose for at least 30 days before Visit 1 (vagal nerve stimulation [VNS] and ketogenic diet do not count as an AED).
6. In the investigator’s opinion, parents or caregivers must be able to keep accurate seizure diaries.
7. Body weight at least 8 kg

E.4

Principal exclusion criteria

1. Presence of progressive neurological disease
2. Presence of drop seizure clusters where individual seizures cannot be reliably counted
3. Prior treatment with perampanel with discontinuation due to safety issues (related to perampanel)
4. Prior treatment with perampanel must have been discontinued at least 30 days before Visit 1
5. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the subject’s safety or study conduct
6. Scheduled for epilepsy-related surgery or any other form of surgery during the projected course of the study
7. Ketogenic diet and VNS, unless stable and ongoing for at least 30 days before Visit 1
8. Treatment with an investigational drug or device in the 30 days before Visit 1
9. Status epilepticus within 12 weeks of Visit 1
10. If felbamate is used as a concomitant AED, subjects must be on felbamate for at least one year, with a stable dose for 60 days before Visit 1. They must not have an indication of hepatic or bone marrow dysfunction while receiving felbamate.
11. Concomitant use of vigabatrin: Subjects who took vigabatrin in the past must be discontinued for at least 5 months before Visit 1, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test
12. 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
13. 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 < 3 times the ULN
14. Adrenocorticotropic hormone within the 6 months before Visit 1
15. Had history of anoxic episodes requiring resuscitation within 6 months before Visit 1
16. Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
17. Females of childbearing potential who:
Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
o Total abstinence
o An intrauterine device or intrauterine hormone-releasing system (IUS)
o An oral contraceptive
o Have a vasectomized partner with confirmed azoospermia.
Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation.
18. Had intermittent use of benzodiazepine of more than 4 single administrations in the month before Visit 1
19. A prolonged QT/QTc interval as demonstrated by a repeated electrocardiogram (ECG)
20. Hypersensitivity to the study drug or any of the excipients
21. Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator(s) would compromise the subject’s ability to safely complete the study
22. Known to be human immunodeficiency virus (HIV) positive
23. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
24. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years
25. History of drug or alcohol dependency or abuse within approximately the last 2 years; use of illegal recreational drugs
26. Concomitant use of medications known to be inducers of cytochrome P450 (CYP3A) including, but not limited to: rifampin, troglitazone, St John’s Wort, efavirenz, nevirapine, glucocorticoids (other than topical usage), modafinil, pioglitazone, and rifabutin
27. Use of AEDs not recommended by Epilepsy Treatment Guidelines for use in LGS including, but not limited to carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine, and vigabatrin
28. Concomitant use of cannabinoids
29. Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 in subjects aged 8 and above.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint will be the median percent change in drop seizure frequency per 28 days.

E.5.1.1

Timepoint(s) of evaluation of this end point

Completion of Core Study

E.5.2

Secondary end point(s)

1. Median percent change in total seizure frequency per 28 days.
2. The 50% responder rate for drop seizures
3. The 50% responder rate for total seizures.
4. Median percent change in non-drop seizure frequency per 28 days.
5. Proportion of subjects with 75%, and 100% responder rates for drop, non -drop, and total seizures.
6. Proportion of subjects with 50% responder rate for non-drop seizures.
7. Physicians’ global evaluation of the subject’s overall changes in symptoms.
8. Incidence of AEs and SAEs, changes in clinical laboratory values, and vital signs.
9. Model-derived average perampanel concentrations.

E.5.2.1

Timepoint(s) of evaluation of this end point

Completion of Core Study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Canada

Czech Republic

France

Hungary

Italy

Japan

Korea, Republic of

Latvia

Poland

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

135

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects are infants & toddlers

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

142

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Expected normal treatment, or switch to commercially available perampanel, or enroll into EAP if activated (for details see protocol section 9.1.3)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-05-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-05-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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