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

Eisai

Status and phase: Terminated; Phase 2

Conditions: Photosensitive Epilepsy

Treatments: Drug: E2082; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03686033

E2082-A001-201

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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8 participants in 6 patient groups

Placebo, E2082 2.5 mg, E2082 25 mg, E2082 40 mg

Experimental group

Description:

Participants will receive a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 1 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 2 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between all the treatment periods.

Treatment:

Drug: E2082

Drug: Placebo

E2082 2.5 mg, E2082 25 mg, Placebo, E2082 40 mg

Experimental group

Description:

Participants will receive a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 1 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 2 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods.

Treatment:

Drug: E2082

Drug: Placebo

E2082 25 mg, Placebo, E2082 2.5 mg, E2082 40 mg

Experimental group

Description:

Participants will receive a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 1 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 2 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods.

Treatment:

Drug: E2082

Drug: Placebo

Placebo, E2082 25 mg, E2082 2.5 mg, E2082 40 mg

Experimental group

Description:

Participants will receive a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 1 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 2 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods.

Treatment:

Drug: E2082

Drug: Placebo

E2082 2.5 mg, Placebo, E2082 25 mg, E2082 40 mg

Experimental group

Description:

Participants will receive a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 1 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 2 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods.

Treatment:

Drug: E2082

Drug: Placebo

E2082 25 mg, E2082 2.5 mg, Placebo, E2082 40 mg

Experimental group

Description:

Participants will receive a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 1 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 2 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods.

Treatment:

Drug: E2082

Drug: Placebo