Lennox-Gastaut Syndrome (LGS)Phase 3NCT02834793
Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
A Phase 3 study testing Perampanel in people with Lennox-Gastaut Syndrome (LGS), run by Eisai Inc. at 65 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Lennox-Gastaut Syndrome (LGS)
- What is being tested?
- Perampanel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 65 sitesin 7 countries
- Study dates
- 13 Dec 2016to 19 Jul 2021
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants must have a diagnosis of LGS as evidenced by:
- more than one type of generalized seizure, including drop seizures (atonic, tonic, or myoclonic) for at least 6 months before Visit 1;
- 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
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- 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)
Who cannot join
- 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
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- 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.
Trial locations and contacts
65 sites in 7 countries.
65 sites in 7 countries
United States31 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342
Austin Epilepsy Care Center
Austin, Texas, 78758
Midatlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
Consultants In Epilepsy and Neurology PLLC
Boise, Idaho, 83702
Cincinnati Children's Hospital Medical Center - PIN
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44195
Children's Hospital of Michigan
Detroit, Michigan, 48201
Wayne State University
Detroit, Michigan, 48201
Mercy Health Saint Mary's Campus
Grand Rapids, Michigan, 49301
Northwest Florida Clinical Research Group, LLC
Gulf Breeze, Florida, 32561
University of Florida Jacksonville
Jacksonville, Florida, 32209
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72202-3500
Pediatric Neurologists of Palm Beach
Loxahatchee Groves, Florida, 33470
Axcess Medical Research
Loxahatchee Groves, Florida
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Nicklaus Children's Hospital
Miami, Florida, 33155
Columbia Saint Mary's
Milwaukee, Wisconsin, 53211
Children's Hospital at Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
Pediatric Neurology PA
Orlando, Florida, 32819
Stanford University
Palo Alto, California, 94304
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
The University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Virginia Commonwealth University
Richmond, Virginia, 23298
Minnesota Epilepsy Group PA
Saint Paul, Minnesota, 55102
Clinical Neurosciences Center
Salt Lake City, Utah, 84132
Road Runner Research Ltd
San Antonio, Texas, 78249
MultiCare Institute for Research and Innovation
Tacoma, Washington, 98405
Baylor Scott and White Research Institute
Temple, Texas, 76508
Carle Foundation Hospital
Urbana, Illinois, 61801
Medical College of Wisconsin
Wauwatosa, Wisconsin, 53226
India9 sites
Synexus Affiliate - Panchshil Hospital
Ahmedabad, Gujarat
Nizams Institute of Medical Sciences
Hyderabad, 500082
Synexus Affiliate - Amrita Institute of Medical Sciences and Research Centre
Kochi, Kerala
Synexus Affiliate - Mallikatta Neuro Center
Mangalore, Karnataka
Synexus Affiliate - Jaslok Hospital and Research Centre
Mumbai, Maharashtra
Synexus Affiliate - Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
Mumbai, Maharashtra
Synexus Affiliate - Sir Ganga Ram Hospital
New Delhi
Synexus Affiliate - Bharati Hospital
Pune, Maharashtra
Synexus Affiliate - Nirmal Hospitals Pvt. Ltd
Surat, Gujarat
Japan8 sites
Eisai Trial Site #1
Fukuoka
Eisai Trial Site #3
Fukuoka
Eisai Trial Site #7
Hakodate
EIsai Trial Site #9
Kagoshima
Eisai Trial Site #4
Niigata
EIsai Trial Site #8
Osaka, 534-0021
Eisai Trial Site #6
Sapporo
Eisai Trial Site #2
Shizuoka
Australia6 sites
Royal Brisbane & Women's Hospital
Brisbane
Austin Health
Heidelberg, Victoria, 3084
Royal Melbourne Hospital
Melbourne
St Vincent's Hospital Melbourne
Melbourne
The Alfred Hospital
Melbourne
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Belgium5 sites
Cliniques Universitaires Saint-Luc
Brussels, Brussels Capital, 1200
Hôpital Erasme
Brussels
UZ Brussel
Jette
Hôpital Universitaire des Enfants Reine Fabiola
La Louvière, Hainaut
Centre Neurologique William Lennox
Ottignies-Louvain-la-Neuve
South Korea4 sites
Kyungpook National University Chilgok hospital
Daegu
Severance Hospital Yonsei University Health System - PPDS
Seoul, 03722
Samsung Medical Center - PPDS
Seoul
Seoul National University Hospital
Seoul
About this study
Official 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
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).
Read the detailed description
This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of perampanel as adjunctive therapy in participants with inadequately controlled seizures associated with LGS. The study will consist of 3 phases: Prerandomization (4 to 8 weeks), Randomization (18 weeks), and an Extension A (52 weeks). An additional Extension B with open-label treatment will be available for optional participation to participants who reside in Japan and in countries where an expanded access program (EAP) cannot be implemented or has not yet been implemented.
- Conditions
- Lennox-Gastaut Syndrome (LGS)
- Being tested
- Placebo, Perampanel
- Keywords
- Lennox-Gastaut Syndrome (LGS), Inadequately controlled seizures
- Medical subject headings
- Lennox Gastaut Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Participants will receive matching placebo in Randomization phase.
PerampanelDrug
Also called E2007
Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B.
| Study group | Role | What they receive |
|---|---|---|
| Perampanel up to 8 mg/day | Experimental | 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. Receives: Drug: Perampanel |
| Matching placebo | Placebo comparator | 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. Receives: Drug: Placebo; Drug: Perampanel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.
Measured: Baseline up to 18 weeks
Secondary outcomes (12)
Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries were used to collect seizure counts and types. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.
Measured: Baseline up to 18 weeks
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
Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. A responder was a participant who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization.
Measured: Baseline up to 18 weeks
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
Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a participant who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization.
Measured: Baseline up to 18 weeks
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)
Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved 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. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.
Measured: Baseline up to 18 weeks
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
Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries were used to collect seizure counts and types. A responder was a participant who experienced a 75% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization.
Measured: Baseline up to 18 weeks
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
Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a participant who experienced a 100% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization.
Measured: Baseline up to 18 weeks
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
Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved 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. A responder was a participant who experienced a 50% or greater reduction in non-drop seizure frequency per 28 days during Maintenance from prerandomization.
Measured: Baseline up to 18 weeks
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase
Assessment of disease severity utilized the CGIC scale at end of treatment to evaluate participants change in disease status from baseline. The CGIC is a 7-point likert scale that measures a physician's global impression of a participants clinical condition. Scale ranged from 1 to 7 with lower score indicated improvement (1=very much improved, 2=much improved, 3=minimally improved), higher score indicated worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicated no change.
Measured: Baseline up to 18 weeks
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
A TEAE was defined as an adverse event with an onset date, or a worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to 28 days following study drug discontinuation. An AE was defined as any untoward medical occurrence in a participant or clinical investigation in a participant administered an investigational product. An AE does not necessarily have a causal relationship with a medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.
Measured: 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)
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Treatment-emergent markedly abnormal value for laboratory values was based Common Terminology Criteria for Adverse events (CTCAE) Version 4.0, and determined as if the post baseline CTCAE Version 4.0 grade increases from baseline and the post baseline grade was >=2 (>=3 for phosphate). Laboratory tests included: Hematology count with differential, Chemistry (Electrolytes, Liver function tests, Renal function parameters, Other: albumin, calcium, cholesterol, globulin, glucose, lactate dehydrogenase, phosphorus, total protein, lipid panel, uric acid), Urinalysis, and Viral tests (Hepatitis B surface antigen, Hepatitis C).
Measured: 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)
Number of Participants With Clinically Significant Vital Signs
Clinically significant means that a value must have met both the criterion value and satisfied the magnitude of change relative to baseline. Vital sign parameters included systolic blood pressure (BP), diastolic BP, pulse rate.
Measured: 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)
Core Study Phase: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study Phase
Due to the early termination of the study resulting in reduced sample size and the variability in treatment response, population pharmacokinetic (PK) analysis and population pharmacokinetic/pharmacodynamic (PK/PD) modeling planned for this study were not conducted and hence data was not collected and analyzed for this outcome measure.
Measured: Up to Week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2016 (estimated)
- Study start13 Dec 2016
- Primary completion26 May 2021
- Study completion19 Jul 2021
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lennox-Gastaut Syndrome (LGS)Studies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02834793
- Sponsor's protocol ID
- E2007-G000-338
- Other IDs
- 2014-002321-35, 2014
- Status last verified
- Mar 2021
- First submitted
- 13 Jul 2016
- Last updated
- 9 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.
PubMed 33825230
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02834793
- Acronym / sponsor ID
- E2007-G000-338
- Conditions
- Lennox-Gastaut Syndrome (LGS)
- Keywords
- Lennox-Gastaut Syndrome (LGS), Inadequately controlled seizures
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Dec 2016 (actual)
- Primary completion
- 26 May 2021 (actual)
- Study completion
- 19 Jul 2021 (actual)
- First posted
- 15 Jul 2016 (estimated)
- Results
- Posted 9 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of perampanel as adjunctive therapy in participants with inadequately controlled seizures associated with LGS. The study will consist of 3 phases: Prerandomization (4 to 8 weeks), Randomization (18 weeks), and an Extension A (52 weeks). An additional Extension B with open-label treatment will be available for optional participation to participants who reside in Japan and in countries where an expanded access program (EAP) cannot be implemented or has not yet been implemented.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perampanel up to 8 mg/day | Experimental | Drug: PerampanelDuring 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. |
| Matching placebo | Placebo comparator | Drug: Placebo, Drug: PerampanelDuring 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Participants must have a diagnosis of LGS as evidenced by:
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants will receive matching placebo in Randomization phase. | Drug | Matching placebo |
| PerampanelAlso: E2007Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B. | Drug | Matching placebo, Perampanel up to 8 mg/day |
Primary outcome
Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Time frame: Baseline up to 18 weeks
Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.
12 secondary outcomes
Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Time frame: Baseline up to 18 weeks
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
Time frame: Baseline up to 18 weeks
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
Time frame: Baseline up to 18 weeks
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)
Time frame: Baseline up to 18 weeks
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
Time frame: Baseline up to 18 weeks
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
Time frame: Baseline up to 18 weeks
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
Time frame: Baseline up to 18 weeks
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase
Time frame: Baseline up to 18 weeks
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: 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)
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Time frame: 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)
Number of Participants With Clinically Significant Vital Signs
Time frame: 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)
Core Study Phase: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study Phase
Time frame: Up to Week 18
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33825230Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
65 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Perampanel in people with Lennox-Gastaut Syndrome (LGS), run by Eisai Inc. at 65 sites in 7 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 9 inclusion and 29 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: stopped early, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, India, Japan, Australia, Belgium and 2 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 9 Mar 2022). 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?
Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline) (time frame: Baseline up to 18 weeks). 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 NCT02834793, which also lists 1 linked publication.
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 9 Mar 2022.