Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03686033
Recruitment Status : Suspended (Safety Review)
First Posted : September 26, 2018
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

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.

Condition or disease Intervention/treatment Phase
Photosensitive Epilepsy Drug: Placebo Drug: E2082 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The study consists of a randomized double-blind design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
Primary Purpose: Treatment
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
Actual Study Start Date : October 31, 2018
Estimated Primary Completion Date : November 18, 2019
Estimated Study Completion Date : November 18, 2019


Arm Intervention/treatment
Experimental: Placebo, E2082 2.5 mg, E2082 25 mg, E2082 40 mg
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
Participants will receive E2082-matched placebo tablets orally.

Drug: E2082
Participants will receive E2082 tablets orally.

Experimental: E2082 2.5 mg, E2082 25 mg, Placebo, E2082 40 mg
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
Participants will receive E2082-matched placebo tablets orally.

Drug: E2082
Participants will receive E2082 tablets orally.

Experimental: E2082 25 mg, Placebo, E2082 2.5 mg, E2082 40 mg
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
Participants will receive E2082-matched placebo tablets orally.

Drug: E2082
Participants will receive E2082 tablets orally.

Experimental: Placebo, E2082 25 mg, E2082 2.5 mg, E2082 40 mg
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
Participants will receive E2082-matched placebo tablets orally.

Drug: E2082
Participants will receive E2082 tablets orally.

Experimental: E2082 2.5 mg, Placebo, E2082 25 mg, E2082 40 mg
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
Participants will receive E2082-matched placebo tablets orally.

Drug: E2082
Participants will receive E2082 tablets orally.

Experimental: E2082 25 mg, E2082 2.5 mg, Placebo, E2082 40 mg
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
Participants will receive E2082-matched placebo tablets orally.

Drug: E2082
Participants will receive E2082 tablets orally.




Primary Outcome Measures :
  1. Mean Change from Baseline in the PPR Range in the Most Sensitive Eye Condition (Eye Closure, Eyes Closed, or Eyes Open Condition) [ Time Frame: 30 minutes to 2 hours pre-dose (Baseline), and at 1, 2, 4, 6, and 8 hours post-dose ]
    PPR is an electroencephalogram (EEG) trait of spike and spike-wave discharges in response to photic stimulation. EEG data will be analyzed to determine the change in PPR following the intake of study treatment.


Secondary Outcome Measures :
  1. Mean Change from Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) [ Time Frame: 30 minutes to 2 hours pre-dose (Baseline), and at 1, 2, 4, 6, and 8 hours post-dose ]
    PPR is an EEG trait of spike and spike-wave discharges in response to photic stimulation. EEG data will be analyzed to determine the change in PPR ranges following the intake of study treatment.

  2. Time to Onset of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) [ Time Frame: 30 minutes to 2 hours pre-dose (Baseline), and at 1, 2, 4, 6, and 8 hours post-dose ]
    Photosensitivity response is essentially intermittent photosensitivity (intermittent photic stimulation [IPS]) assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz (Hz).

  3. Maximum Change from Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) [ Time Frame: 30 minutes to 2 hours pre-dose (Baseline), and at 1, 2, 4, 6, and 8 hours post-dose ]
    Photosensitivity response is essentially intermittent photosensitivity (IPS) assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different Hz.

  4. Duration of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) [ Time Frame: 30 minutes to 2 hours pre-dose (Baseline), and at 1, 2, 4, 6, and 8 hours post-dose ]
    Photosensitivity response is essentially IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different Hz.

  5. Percentage of Participants with Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR). [ Time Frame: 30 minutes to 2 hours pre-dose (Baseline), and at 1, 2, 4, 6, and 8 hours post-dose ]
    Complete suppression, reduction (partial response), and no change (no response) of PPR will be measured. Complete suppression is defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response is defined as a reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response is defined as not meeting complete suppression or partial suppression definitions.

  6. Change from Baseline in Bond and Lader Visual Analogue Scales (BL-VAS). [ Time Frame: Within 2 hours pre-dose (Baseline) and at 1,2,4,6, and 8 hours post-dose ]
    An objective measurement system to assess the extent of damage to the extrapyramidal system and the motor functions that it controls. The Bond-Lader mood rating scale measures CNS-related effects, with scores ranging from 0 to 100. A high score reflects a high level of sedation.

  7. Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Approximately 11 weeks ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

  8. Number of Participants with Clinically Significant Change From Baseline in Vital Signs, Serum Chemistries, Complete Blood Counts, or Liver Function Tests after Single Doses of E2082 Compared to Placebo [ Time Frame: Approximately 11 weeks ]
  9. Maximum Observed Drug Concentration (Cmax) of E2082 [ Time Frame: Up to 8 hours post-dose during each Treatment Visit ]
  10. Time to Reach Maximum Drug Concentration (tmax) of E2082 [ Time Frame: Up to 8 hours post-dose during each Treatment Visit ]
  11. Area Under Concentration-time Curve From Zero to 8 Hours (AUC[0-8h]) [ Time Frame: Up to 8 hours post-dose during each Treatment Visit ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 kilo gram per square meter (kg/m^2) (inclusive) and a total body weight greater than or equal to (>=) 45 kilo gram (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03686033


Locations
Layout table for location information
United States, Arkansas
Clinical Trials, Inc. and Arkansas Epilepsy Program
Little Rock, Arkansas, United States, 72205
United States, Idaho
Consultants in Epilepsy & Neurology, PLLC
Boise, Idaho, United States, 83702
United States, Maryland
Johns Hopkins University- School of Medicine
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University Hospital
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Eisai Inc.

Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03686033     History of Changes
Other Study ID Numbers: E2082-A001-201
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc.:
E2082
Epilepsy
Photosensitive
Anti-epileptic
Seizures
Photoparoxysmal response
PPR
Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsy
Epilepsy, Reflex
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases