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Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome

This study is currently recruiting participants.
Verified November 2017 by Eisai Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02834793
First Posted: July 15, 2016
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Eisai Inc.
July 13, 2016
July 15, 2016
November 21, 2017
December 2016
September 2019   (Final data collection date for primary outcome measure)
Median percent change in drop seizure frequency per 28 days during double-blind treatment (Titration Period and Maintenance Period) relative to the Prerandomization Phase [ Time Frame: up to 18 weeks ]
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.
Same as current
Complete list of historical versions of study NCT02834793 on ClinicalTrials.gov Archive Site
  • Median percent change in total seizure frequency per 28 days during double-blind treatment (Titration Period and Maintenance Period) relative to the Prerandomization Phase [ Time Frame: up to 18 weeks ]
    Percent change from Baseline is calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) * 100.
  • Number of participants with 50% responder rate in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for drop seizures [ Time Frame: up to 12 weeks ]
    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 number of participants who have at least a 50% reduction in seizure frequency during the Maintenance Period relative to the Prerandomization Phase.
  • Number of participants with 50% responder rate in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for total seizures [ Time Frame: up to 12 weeks ]
    The 50% responder rate is defined as the number of participants who have at least a 50% reduction in seizure frequency during the Maintenance Period relative to the Prerandomization Phase.
  • 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 [ Time Frame: up to 18 weeks ]
    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.
  • Number of participants with a 50% responder rate in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for non-drop seizures [ Time Frame: up to 12 weeks ]
    The 50% responder rate is defined as the number 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.
  • Physicians' global evaluation of the participant's overall changes in symptoms at the end of double-blind treatment [ Time Frame: up to 18 weeks ]
    The physician evaluated symptoms using a 7-point Likert scale: 1 = very much improved; and 7 = very much worse.
  • Number of participants with any adverse events (AE) and any Serious adverse events (SAE) [ Time Frame: up to 86 weeks ]
    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.
  • Model-derived average perampanel concentrations at steady state (Cav,ss) during the Maintenance Period of the Core Study [ Time Frame: Days 43, 78, and 126; upon early discontinuation ]
    The average concentration of perampanel in plasma will be measured at the time a "steady state" has been achieved (rates of drug administration and drug elimination are equal).
  • Proportion of participants with 75% and 100% responder rates in the Maintenance Period of the double-blind treatment phase relative to the Prerandomization Phase for drop, non-drop, and total seizures [ Time Frame: up to 12 weeks ]
Same as current
Not Provided
Not Provided
 
Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
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).
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 (22 weeks), and Extension (56 weeks).
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Lennox-Gastaut Syndrome (LGS)
  • Drug: Perampanel
    Other Name: E2007
  • Drug: Placebo
  • Experimental: Perampanel 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 up to a maximum target dose of 8 mg/day according to individual tolerability and efficacy for up to 22 weeks. During the Extension Phase, participants 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.
    Intervention: Drug: Perampanel
  • Placebo Comparator: Matching placebo
    During the Randomization Phase, participants will receive matching placebo for up to 22 weeks. During the Extension Phase, participants who will begin treatment with perampanel in a blinded manner, starting at 2 mg/day and will then be up-titrated to the optimal dose per the investigator's discretion. After the double-blind Conversion Period, participants can be titrated up to 12 mg/day (at 2 week intervals) per the investigator's discretion.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
142
October 2020
September 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants must have a diagnosis of Lennox-Gastaut Syndrome (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.
  • Participants must have been <11 years old at the onset of LGS.
  • Participants must have experienced at least 2 drop seizures per week in the 4-week Baseline Period preceding randomization.
  • Participants must have been receiving 1 to 3 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).
  • In the investigator's opinion, parents or caregivers must be able to keep accurate seizure diaries.
  • Body weight at least 8 kg.

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 must have been discontinued at least 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 in the 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, tiababine, and vigabatrin
  • Concomitant use of cannabinoids
Sexes Eligible for Study: All
2 Years and older   (Child, Adult, Senior)
No
Contact: Eisai Medical Information 1-888-274-2378 esi_medinfo@eisai.com
United States
 
 
NCT02834793
E2007-G000-338
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Not Provided
Eisai Inc.
Eisai Inc.
Not Provided
Not Provided
Eisai Inc.
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP