Clinical trial NCT03686033: A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy
Official title: A Multicenter, Double-Blind, Randomized, Crossover, Single-Dose Study With An Open-Label Treatment Period Evaluating Pharmacodynamic Activity of E2082 in Adult Subjects With Photosensitive Epilepsy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Photosensitive Epilepsy
Keywords: E2082
Epilepsy
Photosensitive
Anti-epileptic
Seizures
Photoparoxysmal response
PPR
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-26
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study consists of a crossover design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period
Secondary outcomes:
measure: 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
timeFrame: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period
measure: 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
timeFrame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
measure: Maximum Change From Baseline of 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
timeFrame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
measure: Duration 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
timeFrame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
measure: Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period
timeFrame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
measure: Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period
timeFrame: Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment period
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
timeFrame: Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
measure: Cmax: Maximum Observed Plasma Concentration for E2082
timeFrame: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
measure: Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082
timeFrame: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
measure: AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082
timeFrame: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Trials, Inc. and Arkansas Epilepsy Program
state: Arkansas
city: Boise
country: United States
facility: Consultants in Epilepsy & Neurology, PLLC
state: Idaho
city: Baltimore
country: United States
facility: Johns Hopkins University- School of Medicine
state: Maryland
city: Saint Louis
country: United States
facility: Washington University Hospital
state: Missouri
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
References: