A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy

A Multicenter, Double-Blind, Randomized, Cross-Over Study Evaluating Pharmacodynamic Activity of E2730 in Adult Subjects With Photosensitive Epilepsy

The primary purpose of the study is to assess the pharmacodynamic (PD) activity of E2730 as measured by suppression of epileptic photoparoxysmal response (PPR) in the participant's most sensitive eye condition in participants with photosensitive epilepsy.

Adult participants with epilepsy will be enrolled in this study. This study will consist of 2 phases: Prerandomization and Randomization Phase.

The Prerandomization Phase will consist of a Screening Period (up to 3 weeks), during which each participant's study eligibility will be determined and baseline assessments will be conducted. The Randomization Phase will consist of 3 Treatment Periods with a single dose in each period (placebo, E2730 40 mg, or E2730 120 mg), each separated by a 3-week washout interval for a total of approximately 6 weeks, and a Follow-up Period (3 weeks after the last dose of study drug).

Inclusion Criteria:

1. Male or female 18 to 60 years old at the time of informed consent.
2. A diagnosis and history of a PPR on EEG with or without a diagnosis of epilepsy.
3. Currently taking up to a maximum of 3 concomitant antiepileptic drugs (AEDs). If taking concomitant AED(s), the dose must have remained stable for at least 4 weeks prior to Screening.
4. A reproducible intermittent photic stimulation (IPS)-induced PPR on EEG of at least 3 points on a frequency assessment scale (SPR) in at least 1 eye condition on at least 3 of the EEGs performed at Screening.
5. A body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2) and a total body weight greater than or equal to 45 kilograms (kg) at the time of Screening.

Exclusion Criteria:

1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test 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.
2. History of nonepileptic seizures (eg, metabolic, structural, or pseudoseizures) while on any antiepileptic medication(s).
3. History of status epilepticus while on any antiepileptic medication(s) within 2 years prior to Screening.
4. Ongoing or history of generalized tonic-clonic seizures within 6 months prior to Screening.
5. Previously developed or who experienced a clinical seizure during prior PPR assessment or Screening IPS procedure, respectively.
6. Use of AEDs that affect gama-aminobutyric acid (GABA) (GABAergic AEDs) (such as tiagabine, vigabatrin, gabapentin, pregabalin) within 3 months prior to Screening.
7. Multiple drug allergies or a severe drug reaction to AED(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
8. An active central nervous system (CNS) infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results.
9. Concomitant use of cannabinoids.
10. Inability to follow restriction on watching television, or use of any device with an animated screen (ie, computer, video games, tablets).
11. A history of prolonged QT syndrome or risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome), or the use of concomitant medications that prolonged the QT/corrected QT (QTc) interval; or prolonged QT/QTc interval (QTc greater than [>] 450 millisecond [msec]) demonstrated on electrocardiograms (ECG) at Screening or baseline (based on average of triplicate ECGs).
12. Any suicidal ideation with intent with or without a plan within 6 months before Screening or during Screening (ie, answering "Yes" to questions 4 or 5 on the suicidal ideation section of the Columbia-Suicide Severity Rating Scale [C-SSRS]).
13. Any lifetime suicidal behavior (per the suicidal behavior section of the C-SSRS).
14. Any 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.
15. Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (eg, increase in spike-wave activity) at Screening.