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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02834793




Registration number
NCT02834793
Ethics application status
Date submitted
13/07/2016
Date registered
15/07/2016
Date last updated
26/07/2019

Titles & IDs
Public title
Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
Scientific title
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
Secondary ID [1] 0 0
2014-002321-35
Secondary ID [2] 0 0
E2007-G000-338
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lennox-Gastaut Syndrome (LGS) 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Perampanel

Experimental: Perampanel up to 8 mg/day - During the Randomization Phase, participants will receive perampanel at a starting dose of 2 milligrams per day (mg/day). Thereafter, the dose will be increased to a maximum target dose of 8 mg/day according to individual tolerability and efficacy for up to 18 weeks. Participants who enter into Extension A will continue to receive perampanel at the dose last received during randomization phase. Participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion.
Participants who continue in Extension B will continue to receive perampanel at the dose last received at the end of Extension A.

Placebo Comparator: Matching placebo - During the Randomization Phase, participants will receive matching placebo for up to 18 weeks.
During the Extension A, participants who received placebo during the Randomization Phase will begin treatment with perampanel in a blinded manner in double-blind Conversion Period, starting at 2 mg/day and then up-titrated to a maximum target dose of 8 mg/day according to individual tolerability and efficacy. After the Conversion Period, participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion.


Treatment: Drugs: Placebo
Participants will receive matching placebo in Randomization phase.

Treatment: Drugs: Perampanel
Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Median percent change in drop seizure frequency per 28 days during double-blind treatment (Titration Period and Maintenance Period) relative to the Prerandomization Phase - Drop seizures are defined as drop attacks or spells involving the entire body, trunk, or head that lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or that could lead to a fall or injury, depending on the participant's position at the time of the attack or spell. Percent change from Baseline is calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) * 100.
Timepoint [1] 0 0
up to 18 weeks
Secondary outcome [1] 0 0
Median percent change in total seizure frequency per 28 days during double-blind treatment (Titration Period and Maintenance Period) relative to the Prerandomization Phase - Percent change from Baseline is calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) * 100.
Timepoint [1] 0 0
up to 18 weeks
Secondary outcome [2] 0 0
Proportion of participants with 50% response in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for drop seizures - Drop seizures are defined as drop attacks or spells involving the entire body, trunk, or head that lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or that could lead to a fall or injury, depending on the participant's position at the time of the attack or spell. The 50% responder rate is defined as the percentage of participants who have at least a 50% reduction in seizure frequency during the Maintenance Period relative to the Prerandomization Phase.
Timepoint [2] 0 0
up to 12 weeks
Secondary outcome [3] 0 0
Proportion of participants with 50% response in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for total seizures - The 50% responder rate is defined as the percentage of participants who have at least a 50% reduction in seizure frequency during the Maintenance Period relative to the Prerandomization Phase.
Timepoint [3] 0 0
up to 12 weeks
Secondary outcome [4] 0 0
Median percent change in non-drop seizure frequency per 28 days during double-blind treatment (Titration Period and Maintenance Period) relative to the Prerandomization Phase - Non-drop seizures are defined as non-drop attacks or spells. Drop attacks and spells involve the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or could lead to a fall or injury, depending on the participant's position at the time of the attack or spell. Percent change from Baseline is calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) * 100.
Timepoint [4] 0 0
up to 18 weeks
Secondary outcome [5] 0 0
Proportion of participants with 75% and 100% response in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for drop, non-drop, and total seizures
Timepoint [5] 0 0
up to 12 weeks
Secondary outcome [6] 0 0
Proportion of participants with 50% response in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for non-drop seizures - The 50% responder rate is defined as the percentage of participants who have at least a 50% reduction in seizure frequency during the Maintenance Period relative to the Prerandomization Phase. Non-drop seizures are defined as non-drop attacks or spells. Drop attacks and spells involve the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or could lead to a fall or injury, depending on the participant's position at the time of the attack or spell.
Timepoint [6] 0 0
up to 12 weeks
Secondary outcome [7] 0 0
Physicians' global evaluation of the participant's overall changes in symptoms at the end of double-blind treatment - The physician evaluated symptoms using a 7-point Likert scale: 1 = very much improved; and 7 = very much worse.
Timepoint [7] 0 0
up to 18 weeks
Secondary outcome [8] 0 0
Number of Participants with any Adverse Events (AEs), Serious Adverse Events (SAEs), Changes in Clinical Laboratory Values, and Vital Signs - For this study, the criteria for identifying AEs are: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product; any new disease or exacerbation of an existing disease; any deterioration in nonprotocol-required measurements of a laboratory value or other clinical test (eg, electrocardiogram [ECG] or X-ray) that results in symptoms, a change in treatment, or discontinuation of study drug; recurrence of an intermittent medical condition (eg, headache) not present pretreatment (Baseline); an abnormal laboratory test result should be considered an AE if the identified laboratory abnormality leads to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not.
Timepoint [8] 0 0
up to 86 weeks
Secondary outcome [9] 0 0
Model-derived average perampanel concentrations at steady state (Cav,ss) during the Maintenance Period of the Core Study
Timepoint [9] 0 0
Days 43, 78, and 126; upon early discontinuation

Eligibility
Key inclusion criteria
- Participants must have a diagnosis of LGS as evidenced by:

1. more than one type of generalized seizure, including drop seizures (atonic,
tonic, or myoclonic) for at least 6 months before Visit 1;

2. an electroencephalogram (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).

- Participants must be at least 2 years old at the time of consent/assent

- Participants must have been <11 years old at the onset of LGS

- Participants must have experienced an average of at least 2 drop seizures per week in
the 4-week Baseline Period preceding randomization

- Participants must have been receiving 1 to 4 concomitant antiepileptic drugs (AEDs) at
a stable dose for at least 30 days before Visit 1 (vagal nerve stimulation (VNS) and
ketogenic diet do not count as AEDs). Use of cannabidiol (CBD) products is allowed and
is counted as one of the 4 maximum allowed concomitant AEDs. CBD dose and product must
have remained stable for at least 30 days before Visit 1 and is to remain the same
throughout the course of the Core Study

- In the investigator's opinion, parents or caregivers must be able to keep accurate
seizure diaries

- Body weight at least 8 kg
Minimum age
2 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Presence of progressive neurological disease

- Presence of drop seizure clusters where individual seizures cannot be reliably counted
(seizure clusters are defined as =2 drop seizures with <5 minutes between any 2
consecutive seizures)

- Prior treatment with perampanel with discontinuation due to safety issues (related to
perampanel)

- Prior treatment with perampanel within 30 days before Visit 1

- Evidence of clinically significant disease (eg, cardiac, respiratory,
gastrointestinal, renal disease, hepatic disease) that in the opinion of the
investigator(s) could affect the participant's safety or study conduct

- Scheduled for epilepsy-related surgery or any other form of surgery during the
projected course of the study

- Ketogenic diet and VNS, unless stable and ongoing for at least 30 days before Visit 1

- Treatment with an investigational drug or device within 30 days before Visit 1

- Status epilepticus within 12 weeks of Visit 1

- If felbamate is used as a concomitant AED, participants must be on felbamate for at
least 1 year, with a stable dose for 60 days before Visit 1. They must not have a
history of white blood cell (WBC) count below =2500/microliters (µL), platelets
<100,000/µL, liver function tests (LFTs) >3 times the upper limit of normal (ULN), or
other indication of hepatic or bone marrow dysfunction while receiving felbamate

- Concomitant use of vigabatrin: participants 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

- 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

- 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

- Adrenocorticotropic hormone within the 6 months before Visit 1

- Had history of anoxic episodes requiring resuscitation within 6 months before Visit 1

- Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
positive beta human chorionic gonadotropin [ß-hCG] with a minimum sensitivity of 25
International Units per Liter (IU/L) or equivalent units of ß-hCG or hCG). 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.

- Females of childbearing potential who: a. had unprotected sexual intercourse within 30
days before study entry and who do not agree to use a highly effective method of
contraception (eg, total abstinence, an intrauterine device, a double-barrier method
[such as condom plus diaphragm with spermicide], a contraceptive implant, an oral
contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout
the entire study period or for 28 days after study drug discontinuation. Females using
hormonal contraceptives containing levogesterol must be on another form of
contraception as well. b. Are currently abstinent, and do not agree to use a
double-barrier method (as described above) or refrain from sexual activity during the
study period or for 28 days after study drug discontinuation. c. Are using hormonal
contraceptives but are not on a stable dose of the same hormonal contraceptive product
for at least 4 weeks before dosing and who do not agree to use the same contraceptive
during the study or for 28 days after study drug discontinuation. (NOTE: All females
will be considered to be of childbearing potential unless they are postmenopausal
[amenorrheic for at least 12 consecutive months, in the appropriate age group, and
without other known or suspected cause] or have been sterilized surgically [i.e.,
bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with
surgery at least 1 month before dosing])

- Had intermittent use of benzodiazepine of more than 4 single administrations in the
month before Visit 1

- A prolonged QT/QTc interval (QTc >450 milliseconds [ms]) as demonstrated by a repeated
electrocardiogram (ECG)

- Hypersensitivity to the study drug or any of the excipients

- Any history of a medical condition or a concomitant medical condition that in the
opinion of the investigator(s) would compromise the participant's ability to safely
complete the study

- Known to be human immunodeficiency virus (HIV) positive

- Active viral hepatitis (B or C) as demonstrated by positive serology at Screening

- 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

- History of drug or alcohol dependency or abuse within approximately the last 2 years;
use of illegal recreational drugs

- 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

- 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

- Participants with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [3] 0 0
St Vincent's Hospital Melbourne - Melbourne
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Florida
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Georgia
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Idaho
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Illinois
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Iowa
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Kentucky
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Louisiana
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Michigan
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Minnesota
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Missouri
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New Jersey
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North Carolina
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Ohio
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Pennsylvania
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Texas
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Virginia
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Washington
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Wisconsin
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Belgium
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Brussels
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Belgium
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Bruxelles
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Jette
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Belgium
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Ottignies-Louvain-la-Neuve
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Czechia
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Poruba
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Czechia
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Praha
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Japan
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Fukuoka
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Japan
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Gifu
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Japan
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Hokkaido
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Japan
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Niigata
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Japan
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Osaka
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Japan
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Sapporo
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Japan
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Shizuoka
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Korea, Republic of
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Daegu
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is being conducted to demonstrate that perampanel given as adjunctive
anti-epileptic treatment is superior to placebo in reducing the number of drop seizures in
participants with inadequately controlled seizures associated with Lennox-Gastaut Syndrome
(LGS).
Trial website
https://clinicaltrials.gov/show/NCT02834793
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Eisai Medical Information
Address 0 0
Country 0 0
Phone 0 0
1-888-274-2378
Fax 0 0
Email 0 0
esi_medinfo@eisai.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02834793