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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02834793
Ethics application status
Date submitted
13/07/2016
Date registered
15/07/2016
Date last updated
9/03/2022

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
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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

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
Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Timepoint [1] 0 0
Baseline up to 18 weeks
Secondary outcome [1] 0 0
Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Timepoint [1] 0 0
Baseline up to 18 weeks
Secondary outcome [2] 0 0
Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures
Timepoint [2] 0 0
Baseline up to 18 weeks
Secondary outcome [3] 0 0
Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Total Seizures
Timepoint [3] 0 0
Baseline up to 18 weeks
Secondary outcome [4] 0 0
Core Study Phase: Median Percent Change in Non-drop Seizure Frequency Per 28 Days During Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline)
Timepoint [4] 0 0
Baseline up to 18 weeks
Secondary outcome [5] 0 0
Core Study Phase: Percentage of Participants With 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures
Timepoint [5] 0 0
Baseline up to 18 weeks
Secondary outcome [6] 0 0
Core Study Phase: Percentage of Participants With 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures
Timepoint [6] 0 0
Baseline up to 18 weeks
Secondary outcome [7] 0 0
Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Non-drop Seizures
Timepoint [7] 0 0
Baseline up to 18 weeks
Secondary outcome [8] 0 0
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase
Timepoint [8] 0 0
Baseline up to 18 weeks
Secondary outcome [9] 0 0
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [9] 0 0
From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)
Secondary outcome [10] 0 0
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Timepoint [10] 0 0
From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)
Secondary outcome [11] 0 0
Number of Participants With Clinically Significant Vital Signs
Timepoint [11] 0 0
From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)
Secondary outcome [12] 0 0
Core Study Phase: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study Phase
Timepoint [12] 0 0
Up to Week 18

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 hertz [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 kilogram (kg)
Minimum age
2 Years
Maximum age
No limit
Sex
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
* Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C -SSRS) in participants aged 8 and above.
* 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
Stopped early
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)
QLD,VIC
Recruitment hospital [1] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment hospital [3] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [5] 0 0
St Vincent's Hospital Melbourne - Melbourne
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussels
Country [20] 0 0
Belgium
State/province [20] 0 0
Hainaut
Country [21] 0 0
Belgium
State/province [21] 0 0
Bruxelles
Country [22] 0 0
Belgium
State/province [22] 0 0
Jette
Country [23] 0 0
Belgium
State/province [23] 0 0
Ottignies-Louvain-la-Neuve
Country [24] 0 0
Czechia
State/province [24] 0 0
Poruba
Country [25] 0 0
Czechia
State/province [25] 0 0
Praha
Country [26] 0 0
India
State/province [26] 0 0
Gujarat
Country [27] 0 0
India
State/province [27] 0 0
Karnataka
Country [28] 0 0
India
State/province [28] 0 0
Kerala
Country [29] 0 0
India
State/province [29] 0 0
Maharashtra
Country [30] 0 0
India
State/province [30] 0 0
Hyderabad
Country [31] 0 0
India
State/province [31] 0 0
New Delhi
Country [32] 0 0
Japan
State/province [32] 0 0
Fukuoka
Country [33] 0 0
Japan
State/province [33] 0 0
Hakodate
Country [34] 0 0
Japan
State/province [34] 0 0
Kagoshima-city
Country [35] 0 0
Japan
State/province [35] 0 0
Niigata
Country [36] 0 0
Japan
State/province [36] 0 0
Osaka
Country [37] 0 0
Japan
State/province [37] 0 0
Sapporo
Country [38] 0 0
Japan
State/province [38] 0 0
Shizuoka
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Daegu
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Seoul

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.