Clinical trial NCT03288129: Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures
Official title: Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Partial Onset Seizures
Secondarily Generalized Seizures
Primary Generalized Tonic-Clonic Seizures
Keywords: monotherapy
adjunctive therapy
open-label
multicenter
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2017-09-19
Enrollment: 54
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the retention rate of perampanel when given as monotherapy or first adjunctive therapy in participants with partial-onset seizures or primary generalized tonic clonic seizures. The study consists of 4 periods: a Screening Period (to start no earlier than 6 weeks before the first dose of study drug), a Titration Period (up to 13 weeks), a Maintenance Period (39 weeks), and a Follow-Up Period (4 weeks).


Eligibility criteria: Inclusion Criteria:

* Participants will be male or female and no younger than 4 years of age and be able to swallow perampanel tablets.
* Participants must have a diagnosis of epilepsy with POS with or without SGS or with PGTCS. Either of the following must have occurred to support an epilepsy diagnosis:

  1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart
  2. One unprovoked (or reflex) seizure with Electroencephalography (EEG) evidence of seizures
* Participants who receive perampanel as a first adjunctive therapy must currently have been treated with stable doses of monotherapy with an anti-epileptic drug (AED) for 8 weeks prior to Visit 2 (Week 0), have not previously received adjunctive AED treatment, and must, in the investigator's judgement, be in need of initial adjunctive therapy after failure to control seizures with AED monotherapy, at the optimal dose and duration.
* Participants who receive perampanel as monotherapy, who were newly diagnosed (treatment naïve), following the defined diagnosis of epilepsy.
* Participants who are currently receiving monotherapy treatment may receive perampanel as monotherapy if, in the investigator's judgment, the participant may benefit from a change in monotherapy treatment. Participants must not have previously received adjunctive AED treatment.
* If antidepressants or antianxiety drugs are used, participants must be on a stable dose regimen of these drugs during the 8 weeks before Visit 2 (Week 0).

Exclusion Criteria:

* Participants should not have previously received or currently be receiving perampanel.
* Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin \[β-hCG\] or hCG test with a minimum sensitivity of 25 International Units per liter \[IU/L\] or equivalent units of β-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:

  * Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

    * Total abstinence (if it is their preferred and usual lifestyle)
    * An intrauterine device or intrauterine hormone-releasing system
    * An oral contraceptive (with additional barrier method if using contraceptive containing levonorgestrel); participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation
    * Have a vasectomized partner with confirmed azoospermia
  * Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation For sites outside of the European Union, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, i.e, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.

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).

* Presence of or previous history of Lennox-Gastaut syndrome
* Presence of non-motor simple partial seizures only
* A history of status epilepticus within 1 year before Screening Visit (Visit 1)
* Participants on antipsychotics or who have psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of attempted suicide within 1 year before Screening Visit (Visit 1)
* Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors
* Concomitant use of barbiturates (except for seizure control indication and premedication for electroencephalogram) and benzodiazepines (except for seizure control indication) within 8 weeks prior to Visit 2 (Week 0)
* Use of intermittent rescue benzodiazepines (i.e, 1 to 2 doses over a 24-hour period is considered a one time rescue) 2 or more times in the 8-week period prior to Visit 2 (Week 0)
* Severe renal insufficiency (defined by estimated glomerular filtration rate of \< 30 milliliters per minute \[mL/min\]) or participants who receive hemodialysis
* 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 NOTE: Stable elevation of liver enzymes, alanine aminotransferase and aspartate aminotransferase due to concomitant medication(s) will be allowed if they are less than 3 times the upper limits of normal.
* Hypersensitivity to perampanel or any excipients
* Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
* Participants who are participating in other interventional clinical trial
* Participant who are judged to have inadequate cognitive ability for participation in the study (intelligence quotient \< 80 or investigator judgment)
* Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS)
* Any lifetime suicidal behavior based on the C-SSRS
* Concomitant use of any form of cannabidiol (CBD)
* Planned brain surgery during study participation

Primary outcomes:
measure: Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment
timeFrame: Month 3
measure: Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment
timeFrame: Month 6
measure: Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment
timeFrame: Month 9
measure: Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment
timeFrame: Month 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period
timeFrame: Up to 39 weeks of Maintenance Period
measure: Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period
timeFrame: Up to 3 months of Maintenance Period
measure: Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period
timeFrame: Up to 6 months of Maintenance Period
measure: Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy
timeFrame: Up to 52 weeks
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAE)
timeFrame: From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Board of Trustees of the University of Alabama for the University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Epilepsy Program
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Epilepsy Center
state: California
city: Palo Alto
country: United States
facility: Stanford Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Jacksonville
country: United States
facility: Baptist Health, Nemours Children's Specialty Care
state: Florida
city: Chicago
country: United States
facility: RUSH University Medical Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: The Regents of The University of Michigan
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Albuquerque
country: United States
facility: UNM Health Providers
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke Neurology
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio
state: Texas
Study officials:
References: