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

NCT03686033 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: E2082-A001-201
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

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.

Conditions

Photosensitive Epilepsy

Keywords

E2082; Epilepsy; Photosensitive; Anti-epileptic; Seizures; Photoparoxysmal response; PPR

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (12)

• 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

  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

  Baseline (30 minutes-2 hours) up to 8 hours postdose 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 Postdose on Day 1 of Each Treatment Period

  Baseline (30 minutes-2 hours) up to 8 hours postdose 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 Postdose on Day 1 of Each Treatment Period

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

• 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

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

Study Arms (6)

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: E2082

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: E2082

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: E2082

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: E2082

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: E2082

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: E2082

Interventions

Placebo DRUG

Participants will receive E2082-matched placebo tablets orally.

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

E2082 DRUG

Participants will receive E2082 tablets orally.

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

Eligibility Criteria

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

You may not qualify if:

• Females who are breastfeeding or pregnant at screening or baseline.
• 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.
• History of nonepileptic seizures (example, metabolic, structural, or pseudoseizures) while on any antiepileptic medication.
• History of status epilepticus while on any antiepileptic medication(s) within 2 years before screening.
• Ongoing or history of generalized tonic-clonic seizures (GTCS) within 6 months before screening.
• Participants who had developed a clinical seizure during previous PPR assessment, or who experiences a clinical seizure during the Screening IPS procedure.
• Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (example, increase in spike-wave activity) at screening.
• 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.
• Use of perampanel within 6 weeks before screening.
• Use of felbamate for less than 2 years or where the dose has not been stable for at least 8 weeks before Visit 1.
• Use of vigabatrin within 5 months before screening and/or documented evidence of vigabatrin associated clinically significant abnormality in a visual perimetry test.
• 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.
• Concomitant use of cannabinoids.
• Use of concomitant potent cytochrome P450 (CYP)3A inducers or inhibitors within 4 weeks or 5 half-lives, whichever is longer.
• Vagus nerve stimulation (VNS) implanted within 5 months or changes in parameter within 4 weeks before 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

University 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

Limitations and Caveats

The study was terminated due to safety concerns from a phase 1 study (E2082-J081-001; NCT03402178) and preclinical animal toxicity testing.

Results Point of Contact

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

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study consists of a randomized double-blind design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of a crossover design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 26, 2018
• Study Start: October 31, 2018
• Primary Completion: June 18, 2019
• Study Completion: June 18, 2019
• Last Updated: September 28, 2020
• Results First Posted: September 28, 2020

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

US (5)