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The study was stopped due to efficacy reasons.
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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.
Adult participants with epilepsy will be enrolled in this study. This study will consist of 2 phases: Prerandomization and Randomization Phase.
The Prerandomization Phase will consist of a Screening Period (up to 3 weeks), during which each participant's study eligibility will be determined and baseline assessments will be conducted. The Randomization Phase will consist of 3 Treatment Periods with a single dose in each period (placebo, E2730 40 mg, or E2730 120 mg), each separated by a 3-week washout interval for a total of approximately 6 weeks, and a Follow-up Period (3 weeks after the last dose of study drug).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Placebo, E2730 120 mg, E2730 40 mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Participants will receive E2730-matched placebo capsule, orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Photosensitivity described the presentation of an epileptiform EEG response PPR from exposure to IPS. SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. 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). 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. Lower scores represented better outcomes. Mean change from baseline in the SPR in each of the 3 eye conditions (Eye Closure, Eyes Closed, and Eyes Opened) was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Eisai Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trials, Inc. and Arkansas Epilepsy Program | Little Rock | Arkansas | 72205 | United States | ||
| Consultants in Epilepsy & Neurology, PLLC |
A total of 8 participants were screened, of which 2 were screen failures and 6 were randomized to receive study treatment. The study was terminated due to lack of photoparoxysmal response (PPR).
Participants took part in the study at 4 investigative sites in the United States from 27 July 2018 to 14 February 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Placebo + E2730 40 mg + E2730 120 mg | Participants received, E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 40 milligram (mg) (Treatment B) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| FG001 | Sequence 2: E2730 40 mg + E2730 120 mg + Placebo | Participants received, E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| FG002 | Sequence 3: E2730 120 mg + Placebo + E2730 40 mg | Participants received, E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 -matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| FG003 | Sequence 4: Placebo + E2730 120 mg + E2730 40 mg | Participants received, E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| FG004 | Sequence 5: E2730 40 mg + Placebo + E2730 120 mg | Participants received, E2730 40 mg (Treatment B) capsule, once on Day 1 in Treatment Period 1, followed by E2730 -matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| FG005 | Sequence 6: E2730 120 mg + E2730 40 mg + Placebo | Participants received, E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Day 1) |
| |||||||||||||
| Washout Period (at Least 3 Weeks) |
| |||||||||||||
| Treatment Period 2 (Day 1) |
| |||||||||||||
| Washout Period (at Least 3 Weeks) |
| |||||||||||||
| Treatment Period 3 (Day 1) |
|
The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Participants received E2730-matched placebo (Treatment A) or E2730 40 mg (Treatment B) or E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1 to 3 as per assigned treatment sequence. A washout period of at least 3 weeks was maintained between all the treatment periods. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | The pharmacodynamic (PD) analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Mean | Standard Deviation | units on a scale | Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period |
Up to 28 days after last dose of study drug (Day 71)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A: Placebo | Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eyelid myoclonus | Eye disorders | MedDRA Version 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | +1-888-274-2378 | esi_medinfo@eisai.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 17, 2018 | Feb 11, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 13, 2019 | Feb 11, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020195 | Epilepsy, Reflex |
| D004827 | Epilepsy |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
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Not provided
Not provided
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Not provided
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.
|
| 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. |
|
| 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. |
|
| E2730 | Drug | Participants will receive E2730 capsule, orally. |
|
| 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 | 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 change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially 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) 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 | Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean change from baseline SPR data across participants. Duration of suppression was defined as the difference in hours between the onset of suppression and the end of suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants (not for each participant) 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 of at least 3 units lower than the mean SPR at baseline. SPR was a standardized derived measure of range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14. Lower scores represented better outcomes. | 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 | 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 the response not meeting complete suppression or partial suppression definitions. | 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 | Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) across participants (not for each participant) were reported. Photosensitivity described the presentation of an epileptiform EEG response (PPR) from exposure to IPS. SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. 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). 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. Lower scores representing better outcomes. | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE is continuous. An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) |
| Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs | Vital signs parameters included systolic and diastolic Blood Pressure, pulse rate, respiratory rate, and temperature were assessed. Clinically significant values were defined as values above or below the normal reference range post-dose. Number of participants with clinically significant change from baseline values for vital signs was reported. | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) |
| Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Laboratory assessment included clinical chemistry, hematology and liver function test parameters. Clinically significant values were defined as values above or below the normal reference range post-dose. Number of participants with clinically significant change from baseline values for laboratory parameters: clinical chemistry, hematology and liver function test are reported. | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) |
| Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite | Days 1, 22 and 43: 0-8 hours post-dose |
| Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite | Days 1, 22 and 43: 0-8 hours post-dose |
| AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite | Days 1, 22 and 43: 0-8 hours post-dose |
| Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity | Relationship between PK parameters of E2730 and PD parameters (onset, maximum change, and duration of impact on photosensitivity) were to be assessed using model-based approach. The PK-PD analysis dataset were to be used and included in examination of the relationship of PK of E2730 and change in PPR response (example, time of onset, maximum change, and duration of PPR; Bond and Lader data). | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period |
| Boise |
| Idaho |
| 83702 |
| United States |
| Johns Hopkins University- School of Medicine | Baltimore | Maryland | 21287 | United States |
| Washington University Hospital | St Louis | Missouri | 63110 | United States |
| Unniversity of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
|
| Secondary | 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 | Photosensitivity described the presentation of an epileptiform EEG response PPR from exposure to IPS. SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. 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). 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. Lower scores represented better outcomes. Mean change from baseline in the SPR in each of the 3 eye conditions (Eye Closure, Eyes Closed, and Eyes Opened) was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3). | The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Mean | Standard Deviation | units on a scale | Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose 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 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) was determined from mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially 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. | The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Number | hours | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose 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 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) was determined from mean change from baseline SPR data across participants. Duration of suppression was defined as the difference in hours between the onset of suppression and the end of suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants (not for each participant) 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 of at least 3 units lower than the mean SPR at baseline. SPR was a standardized derived measure of range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14. Lower scores represented better outcomes. | The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Number | hours | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period |
|
|
|
| Secondary | 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 | 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 the response not meeting complete suppression or partial suppression definitions. | The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Count of Participants | Participants | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose 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 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) across participants (not for each participant) were reported. Photosensitivity described the presentation of an epileptiform EEG response (PPR) from exposure to IPS. SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. 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). 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. Lower scores representing better outcomes. | The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Number | units on a scale | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE is continuous. An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. | Posted | Count of Participants | Participants | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs | Vital signs parameters included systolic and diastolic Blood Pressure, pulse rate, respiratory rate, and temperature were assessed. Clinically significant values were defined as values above or below the normal reference range post-dose. Number of participants with clinically significant change from baseline values for vital signs was reported. | The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. | Posted | Count of Participants | Participants | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Laboratory assessment included clinical chemistry, hematology and liver function test parameters. Clinically significant values were defined as values above or below the normal reference range post-dose. Number of participants with clinically significant change from baseline values for laboratory parameters: clinical chemistry, hematology and liver function test are reported. | The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. | Posted | Count of Participants | Participants | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite | The pharmacokinetic (PK) analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Days 1, 22 and 43: 0-8 hours post-dose |
|
|
|
| Secondary | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite | The PK analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Median | Full Range | hours | Days 1, 22 and 43: 0-8 hours post-dose |
|
|
|
| Secondary | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite | The PK analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Days 1, 22 and 43: 0-8 hours post-dose |
|
|
|
| Secondary | Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity | Relationship between PK parameters of E2730 and PD parameters (onset, maximum change, and duration of impact on photosensitivity) were to be assessed using model-based approach. The PK-PD analysis dataset were to be used and included in examination of the relationship of PK of E2730 and change in PPR response (example, time of onset, maximum change, and duration of PPR; Bond and Lader data). | The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. | Posted | Number | correlation coefficient | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 3 |
| 5 |
| EG001 | Treatment B: E2730 40 mg | Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG002 | Treatment C: E2730 120 mg | Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. | 0 | 5 | 1 | 5 | 0 | 5 |
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA Version 21.1 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
|
Not provided
Not provided
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
|
| Eyes Closed: At Baseline |
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| Eyes Closed: Change at 8 hours post-dose |
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| Eyes Open: At Baseline |
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| Eyes Open: Change at 8 hours post-dose |
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In eye closure condition. The mixed effects model for the crossover part of the study will include treatment, period, and sequence as fixed effects, baseline (Predose) measurement as a covariate, and subject nested within sequence as a random effect. |
| LS Mean Difference |
| 0.30 |
| 2-Sided |
| 90 |
| -0.60 |
| 1.21 |
| Superiority |
| In eyes closed condition. The mixed effects model for the crossover part of the study will include treatment, period, and sequence as fixed effects, baseline (Predose) measurement as a covariate, and subject nested within sequence as a random effect. | LS Mean Difference | 1.62 | 2-Sided | 90 | -1.16 | 4.39 | Superiority |
| In eyes closed condition. The mixed effects model for the crossover part of the study will include treatment, period, and sequence as fixed effects, baseline (Predose) measurement as a covariate, and subject nested within sequence as a random effect. | LS Mean Difference | 1.05 | 2-Sided | 90 | -0.89 | 2.98 | Superiority |
| In eyes open condition. The mixed effects model for the crossover part of the study will include treatment, period, and sequence as fixed effects, baseline (Predose) measurement as a covariate, and subject nested within sequence as a random effect. | LS Mean Difference | 0.21 | 2-Sided | 90 | -1.87 | 2.28 | Superiority |
| In eyes open condition. The mixed effects model for the crossover part of the study will include treatment, period, and sequence as fixed effects, baseline (Predose) measurement as a covariate, and subject nested within sequence as a random effect. | LS Mean Difference | 1.27 | 2-Sided | 90 | -0.57 | 3.11 | Superiority |
| Eyes Closed |
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| Eyes Opened |
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| Eyes Closed: Duration |
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| Eyes Open: Duration |
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| No Response |
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| Eyes Closed: Baseline |
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| Eyes Closed: Maximum change from baseline |
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| Eyes Open: Baseline |
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| Eyes Open: Maximum change from baseline |
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| Title | Measurements |
|---|---|
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| Liver Function Test |
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