A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy

Phase 2TerminatedNCT03686033

Eisai Inc.8 enrolled

Overview

The primary purpose of the study is to assess pharmacodynamic (PD) activity of E2082 as measured by suppression of epileptic photoparoxysmal response (PPR) in the participant's most sensitive eye condition in participants with photosensitive epilepsy, compared to placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Photosensitive Epilepsy

Interventions

PlaceboDRUG

Participants will receive E2082-matched placebo tablets orally.

E2082DRUG

Participants will receive E2082 tablets orally.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

1. Diagnosis and/or history of a PPR on EEG. 2. If currently being treated with antiepileptic drug (AED), up to a maximum of 3 concomitant AEDs is allowed provided that doses must have remained stable for at least 4 weeks (or at least 8 weeks if recently initiated) before screening. 3. Reproducible IPS-induced PPR on EEG of at least 3 points on the SPR scale in at least 1 eye condition (eye closure, eyes closed, eyes open) on at least 3 of the EEGs performed at screening. 4. Body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m\^2) (inclusive) and a total body weight greater than or equal to (\>=) 45 kilogram (kg) at screening. 5. Agrees to refrain from strenuous exercise and alcohol consumption during the 24-hour period before screening and before each treatment day. Exclusion Criteria: 1. Females who are breastfeeding or pregnant at screening or baseline. 2. Male participants who have not had a successful vasectomy, they and their female partners not of childbearing potential, or practicing highly effective contraception throughout the study period and for 28 days after study drug discontinuation. No sperm donation is allowed during the study period and for 28 days after study drug discontinuation. 3. History of nonepileptic seizures (example, metabolic, structural, or pseudoseizures) while on any antiepileptic medication. 4. History of status epilepticus while on any antiepileptic medication(s) within 2 years before screening. 5. Ongoing or history of generalized tonic-clonic seizures (GTCS) within 6 months before screening. 6. Participants who had developed a clinical seizure during previous PPR assessment, or who experiences a clinical seizure during the Screening IPS procedure. 7. Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (example, increase in spike-wave activity) at screening. 8. Inability to follow restriction on watching television, or use of any device(s) with an animated screen (example, computer, video games, tablets, or smart phone) from the time of arrival at the study center until study procedures are completed for that day. 9. Use of perampanel within 6 weeks before screening. 10. Use of felbamate for less than 2 years or where the dose has not been stable for at least 8 weeks before Visit 1. 11. Use of vigabatrin within 5 months before screening and/or documented evidence of vigabatrin associated clinically significant abnormality in a visual perimetry test. 12. Use of benzodiazepines for non-epilepsy related indications. Intermittent use of benzodiazepines as rescue medication or stable dosage (greater than 4 weeks before screening) for epilepsy indications is allowed. 13. Concomitant use of cannabinoids. 14. Use of concomitant potent cytochrome P450 (CYP)3A inducers or inhibitors within 4 weeks or 5 half-lives, whichever is longer. 15. Vagus nerve stimulation (VNS) implanted within 5 months or changes in parameter within 4 weeks before screening. 16. On a ketogenic diet for which the diet is not a stable regimen for at least 4 weeks before screening. 17. Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 18. A history of prolonged QT syndrome or risk factors for torsade de pointes, or the use of concomitant medications that cause QT prolongation as demonstrated on screening electrocardiogram (ECG). 19. Any suicidal ideation with intent with or without a plan within 6 months before or during screening, and/or any lifetime suicidal behavior. 20. Any psychotic disorder(s) or unstable recurrent affective disorders.

Locations (5)

Clinical Trials, Inc. and Arkansas Epilepsy Program

Little Rock, Arkansas, United States

Consultants in Epilepsy & Neurology, PLLC

Boise, Idaho, United States

Johns Hopkins University- School of Medicine

Baltimore, Maryland, United States

Washington University Hospital

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period

PPR was an electroencephalogram (EEG) trait of spike and spike-wave discharges in response to photic stimulation. Intermittent photic stimulation (IPS)-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 hertz (Hz). The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, standard photosensitivity response (SPR) was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. Most sensitive eye condition was defined as one that yielded the largest SPR before dosing.

Time frame: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period

Secondary Outcomes

Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period

PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes.

Time frame: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period

Time to Onset of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.