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

NCT03603639 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: E2730-A001-201
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Photosensitive Epilepsy

Keywords

E2730; Epilepsy; Photosensitive; Seizures; PPR; Anti-epileptic

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in the Standard Photosensitivity Response (SPR) in the Most Sensitive Eye Condition at 8 Hours Post-dose on Day 1 of Each Treatment Period

  Photosensitivity described the presentation of an epileptiform electroencephalogram (EEG) response PPR from exposure to intermittent photic stimulation (IPS). SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The participants were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14 between the lowest to the highest frequencies of IPS that elicits epileptiform activity by EEG. The lower scores represented better outcomes. Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. Mean change from baseline in the SPR most sensitive eye condition was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3).

  Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period

Secondary Outcomes (12)

• Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period

  Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose 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 Post-dose on Day 1 of Each Treatment Period

  Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period

• Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period

  Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period

• Number of Participants With Complete Suppression, Partial Response, and no Response of SPR up to 8 Hours Post-dose on Day 1 of Each Treatment Period

  Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period

• 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 Post-dose on Day 1 of Each Treatment Period

  Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period

Study Arms (6)

Placebo, E2730 40 mg, E2730 120 mg

EXPERIMENTAL

Participants will receive a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 1 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 2 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.

Drug: Placebo; Drug: E2730

E2730 40 mg, E2730 120 mg, Placebo

EXPERIMENTAL

Participants will receive a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 1 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 2 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.

Drug: Placebo; Drug: E2730

E2730 120 mg, Placebo, E2730 40 mg

EXPERIMENTAL

Participants will receive a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 1 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 2 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.

Drug: Placebo; Drug: E2730

Placebo, E2730 120 mg, E2730 40 mg

EXPERIMENTAL

Participants will receive a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 1 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 2 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.

Drug: Placebo; Drug: E2730

E2730 40 mg, Placebo, E2730 120 mg

EXPERIMENTAL

Participants will receive a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 1 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 2 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.

Drug: Placebo; Drug: E2730

E2730 120 mg, E2730 40 mg, Placebo

EXPERIMENTAL

Participants will receive a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 1 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 2 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.

Drug: Placebo; Drug: E2730

Interventions

Placebo DRUG

Participants will receive E2730-matched placebo capsule, orally.

E2730 120 mg, E2730 40 mg, Placebo; E2730 120 mg, Placebo, E2730 40 mg; E2730 40 mg, E2730 120 mg, Placebo; E2730 40 mg, Placebo, E2730 120 mg; Placebo, E2730 120 mg, E2730 40 mg; Placebo, E2730 40 mg, E2730 120 mg

E2730 DRUG

Participants will receive E2730 capsule, orally.

E2730 120 mg, E2730 40 mg, Placebo; E2730 120 mg, Placebo, E2730 40 mg; E2730 40 mg, E2730 120 mg, Placebo; E2730 40 mg, Placebo, E2730 120 mg; Placebo, E2730 120 mg, E2730 40 mg; Placebo, E2730 40 mg, E2730 120 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female 18 to 60 years old at the time of informed consent.
• A diagnosis and history of a PPR on EEG with or without a diagnosis of epilepsy.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• History of nonepileptic seizures (eg, metabolic, structural, or pseudoseizures) while on any antiepileptic medication(s).
• History of status epilepticus while on any antiepileptic medication(s) within 2 years prior to Screening.
• Ongoing or history of generalized tonic-clonic seizures within 6 months prior to Screening.
• Previously developed or who experienced a clinical seizure during prior PPR assessment or Screening IPS procedure, respectively.
• Use of AEDs that affect gama-aminobutyric acid (GABA) (GABAergic AEDs) (such as tiagabine, vigabatrin, gabapentin, pregabalin) within 3 months prior to Screening.
• Multiple drug allergies or a severe drug reaction to AED(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
• 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.
• Concomitant use of cannabinoids.
• Inability to follow restriction on watching television, or use of any device with an animated screen (ie, computer, video games, tablets).
• 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).
• 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 \[C-SSRS\]).
• Any lifetime suicidal behavior (per the suicidal behavior section of the C-SSRS).
• 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.
• Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (eg, increase in spike-wave activity) at Screening.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (5)

Clinical Trials, Inc. and Arkansas Epilepsy Program

Little Rock, Arkansas, 72205, United States

Location

Consultants in Epilepsy & Neurology, PLLC

Boise, Idaho, 83702, United States

Location

Johns Hopkins University- School of Medicine

Baltimore, Maryland, 21287, United States

Location

Washington University Hospital

St Louis, Missouri, 63110, United States

Location

Unniversity of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Epilepsy, Reflex; Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Study Officials

• Medical Director

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 27, 2018
• Study Start: July 27, 2018
• Primary Completion: February 14, 2019
• Study Completion: February 14, 2019
• Last Updated: May 4, 2022
• Results First Posted: May 4, 2022

Record last verified: 2022-04

Locations

US (5)