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

Photosensitive Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03686033
• Other study ID #: E2082-A001-201
• Status: Terminated
• Phase: Phase 2
• Start date: October 31, 2018
• Est. completion date: June 18, 2019

Study information

• Verified date: August 2018
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: June 18, 2019
• Est. primary completion date: June 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Photosensitive Epilepsy

Intervention

Drug:
• Placebo
Participants will receive E2082-matched placebo tablets orally.
• E2082
Participants will receive E2082 tablets orally.

Locations

Country	Name	City	State
United States	Johns Hopkins University- School of Medicine	Baltimore	Maryland
United States	Consultants in Epilepsy & Neurology, PLLC	Boise	Idaho
United States	Clinical Trials, Inc. and Arkansas Epilepsy Program	Little Rock	Arkansas
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	PPR was an EEG trait of spike and spike-wave discharges in response to 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 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes.	Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period
Secondary	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	Time to onset of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean Response of standardized photosensitivity response (SPR) across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were 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.	Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Secondary	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	Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) were reported. PPR was an EEG trait of spike and spike-wave discharges in response to 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 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes.	Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Secondary	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	Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. Duration of mean suppression was defined as the difference in hours between the onset of mean suppression and the end of mean suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants was at least 3 units below the mean SPR at baseline. The end of mean suppression was defined as the last time (second time) with two successive reductions in mean SPR across participants of at least 3 units lower than the mean SPR at baseline. Photosensitivity response were essentially IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz.	Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Secondary	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	Complete suppression, reduction (partial response), and no change (no response) of PPR will be measured. Complete suppression was defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response was 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 was defined as not meeting complete suppression or partial suppression definitions.	Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Secondary	Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period	BL-VAS system was used to assess the extent of damage to the extrapyramidal system and the motor functions that it controls. The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 millimeter (mm) about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three subscales: a.) Anxiety, b.) Dysphoria, c.) sedation with each item ranges from 0 to 100 and higher scores indicated better condition.	Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment period
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
Secondary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs		Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
Secondary	Number of Participants With Clinically Significant Change From Baseline in Laboratory Values		Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
Secondary	Cmax: Maximum Observed Plasma Concentration for E2082		Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
Secondary	Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082		Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
Secondary	AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082		Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period