Photosensitive Epilepsy
Conditions
Keywords
E2730, Epilepsy, Photosensitive, Seizures, PPR, Anti-epileptic
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.
Detailed description
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).
Interventions
DRUGPlacebo
Participants will receive E2730-matched placebo capsule, orally.
DRUGE2730
Participants will receive E2730 capsule, orally.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 18 to 60 years old at the time of informed consent. 2. A diagnosis and history of a PPR on EEG with or without a diagnosis of epilepsy. 3. 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. 4. 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. 5. 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.
Exclusion criteria
1. 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. 2. History of nonepileptic seizures (eg, metabolic, structural, or pseudoseizures) while on any antiepileptic medication(s). 3. History of status epilepticus while on any antiepileptic medication(s) within 2 years prior to Screening. 4. Ongoing or history of generalized tonic-clonic seizures within 6 months prior to Screening. 5. Previously developed or who experienced a clinical seizure during prior PPR assessment or Screening IPS procedure, respectively. 6. Use of AEDs that affect gama-aminobutyric acid (GABA) (GABAergic AEDs) (such as tiagabine, vigabatrin, gabapentin, pregabalin) within 3 months prior to Screening. 7. Multiple drug allergies or a severe drug reaction to AED(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions. 8. 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. 9. Concomitant use of cannabinoids. 10. Inability to follow restriction on watching television, or use of any device with an animated screen (ie, computer, video games, tablets). 11. 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). 12. 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 \[C-SSRS\]). 13. Any lifetime suicidal behavior (per the suicidal behavior section of the C-SSRS). 14. 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. 15. Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (eg, increase in spike-wave activity) at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (30 minutes-2 hours) pre-dose and 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) | 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. |
| 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 | 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). |
| Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) | 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. |
| 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 | Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period | 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). |
| Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs | First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in the United States from 27 July 2018 to 14 February 2019.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Washout Period (at Least 3 Weeks) | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout Period (at Least 3 Weeks) | Study terminated by sponsor | 0 | 0 | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 7.32 |
| Age, Customized >= 40 to < 60 | 1 Participants |
| Age, Customized greater than or equal to (>=) 18 to less than (<) 40 | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 3 / 5 | 1 / 4 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 | 1 / 5 |
Outcome results
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).
Time frame: Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Placebo | 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 | Baseline | 7.80 units on a scale | Standard Deviation 5.495 |
| Treatment A: Placebo | 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 | Change at 8 hour post-dose | -0.12 units on a scale | Standard Deviation 1.677 |
| Treatment B: E2730 40 mg | 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 | Baseline | 5.50 units on a scale | Standard Deviation 6.137 |
| Treatment B: E2730 40 mg | 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 | Change at 8 hour post-dose | 0.65 units on a scale | Standard Deviation 0.755 |
| Treatment C: E2730 120 mg | 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 | Baseline | 9.00 units on a scale | Standard Deviation 3.391 |
| Treatment C: E2730 120 mg | 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 | Change at 8 hour post-dose | 1.00 units on a scale | Standard Deviation 2.839 |
Comparison: 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.90% CI: [-0.72, 3.48]
Comparison: 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.90% CI: [-0.49, 2.63]
Secondary
AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite
Time frame: Days 1, 22 and 43: 0-8 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Placebo | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite | E2730 | 5140 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 18.4 |
| Treatment A: Placebo | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite | N-acetyl metabolite | 2.48 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 183 |
| Treatment B: E2730 40 mg | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite | E2730 | 15100 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.2 |
| Treatment B: E2730 40 mg | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite | N-acetyl metabolite | 10.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 37.3 |
Secondary
Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite
Time frame: Days 1, 22 and 43: 0-8 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Placebo | Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite | E2730 | 737 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18.4 |
| Treatment A: Placebo | Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite | N-acetyl metabolite | 0.672 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 62.3 |
| Treatment B: E2730 40 mg | Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite | E2730 | 2440 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18.5 |
| Treatment B: E2730 40 mg | Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite | N-acetyl metabolite | 1.89 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.2 |
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.
Time frame: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Placebo | 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 | Eyes Closed: Duration | NA hours |
| Treatment A: Placebo | 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 | Eye Closure: Duration | NA hours |
| Treatment A: Placebo | 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 | Eyes Open: Duration | NA hours |
| Treatment B: E2730 40 mg | 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 | Eyes Closed: Duration | NA hours |
| Treatment B: E2730 40 mg | 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 | Eye Closure: Duration | NA hours |
| Treatment B: E2730 40 mg | 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 | Eyes Open: Duration | NA hours |
| Treatment C: E2730 120 mg | 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 | Eye Closure: Duration | NA hours |
| Treatment C: E2730 120 mg | 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 | Eyes Open: Duration | NA hours |
| Treatment C: E2730 120 mg | 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 | Eyes Closed: Duration | NA hours |
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.
Time frame: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Placebo | 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 | Eye Closure: Baseline | 14.0 units on a scale |
| Treatment A: Placebo | 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 | Eye Closure: Maximum change from baseline | 2.6 units on a scale |
| Treatment A: Placebo | 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 | Eyes Closed: Baseline | 13.0 units on a scale |
| Treatment A: Placebo | 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 | Eyes Closed: Maximum change from baseline | 1.6 units on a scale |
| Treatment A: Placebo | 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 | Eyes Open: Baseline | 11.0 units on a scale |
| Treatment A: Placebo | 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 | Eyes Open: Maximum change from baseline | 3.8 units on a scale |
| Treatment B: E2730 40 mg | 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 | Eyes Open: Maximum change from baseline | 2.2 units on a scale |
| Treatment B: E2730 40 mg | 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 | Eye Closure: Baseline | 14.0 units on a scale |
| Treatment B: E2730 40 mg | 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 | Eyes Closed: Maximum change from baseline | 2.4 units on a scale |
| Treatment B: E2730 40 mg | 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 | Eyes Open: Baseline | 13.0 units on a scale |
| Treatment B: E2730 40 mg | 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 | Eye Closure: Maximum change from baseline | 2.0 units on a scale |
| Treatment B: E2730 40 mg | 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 | Eyes Closed: Baseline | 13.0 units on a scale |
| Treatment C: E2730 120 mg | 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 | Eye Closure: Maximum change from baseline | 4.0 units on a scale |
| Treatment C: E2730 120 mg | 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 | Eyes Closed: Baseline | 12.0 units on a scale |
| Treatment C: E2730 120 mg | 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 | Eyes Open: Maximum change from baseline | 5.0 units on a scale |
| Treatment C: E2730 120 mg | 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 | Eyes Closed: Maximum change from baseline | 6.0 units on a scale |
| Treatment C: E2730 120 mg | 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 | Eye Closure: Baseline | 13.0 units on a scale |
| Treatment C: E2730 120 mg | 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 | Eyes Open: Baseline | 10.0 units on a scale |
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).
Time frame: Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Placebo | 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 | Eye Closure: At Baseline | 8.00 units on a scale | Standard Deviation 6 |
| Treatment A: Placebo | 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 | Eye Closure: Change at 8 hours post-dose | 0.12 units on a scale | Standard Deviation 1.579 |
| Treatment A: Placebo | 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 | Eyes Closed: At Baseline | 7.60 units on a scale | Standard Deviation 5.225 |
| Treatment A: Placebo | 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 | Eyes Closed: Change at 8 hours post-dose | -0.24 units on a scale | Standard Deviation 1.711 |
| Treatment A: Placebo | 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 | Eyes Open: At Baseline | 4.20 units on a scale | Standard Deviation 5.762 |
| Treatment A: Placebo | 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 | Eyes Open: Change at 8 hours post-dose | 0.76 units on a scale | Standard Deviation 1.846 |
| Treatment B: E2730 40 mg | 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 | Eyes Open: Change at 8 hours post-dose | 0.05 units on a scale | Standard Deviation 1.716 |
| Treatment B: E2730 40 mg | 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 | Eye Closure: At Baseline | 5.75 units on a scale | Standard Deviation 6.551 |
| Treatment B: E2730 40 mg | 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 | Eyes Closed: Change at 8 hours post-dose | 0.90 units on a scale | Standard Deviation 1.149 |
| Treatment B: E2730 40 mg | 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 | Eyes Open: At Baseline | 4.75 units on a scale | Standard Deviation 6.185 |
| Treatment B: E2730 40 mg | 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 | Eye Closure: Change at 8 hours post-dose | 0.65 units on a scale | Standard Deviation 1.279 |
| Treatment B: E2730 40 mg | 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 | Eyes Closed: At Baseline | 5.25 units on a scale | Standard Deviation 6.021 |
| Treatment C: E2730 120 mg | 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 | Eye Closure: Change at 8 hours post-dose | 0.60 units on a scale | Standard Deviation 2.054 |
| Treatment C: E2730 120 mg | 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 | Eyes Closed: At Baseline | 8.80 units on a scale | Standard Deviation 3.114 |
| Treatment C: E2730 120 mg | 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 | Eyes Open: Change at 8 hours post-dose | 1.20 units on a scale | Standard Deviation 2.874 |
| Treatment C: E2730 120 mg | 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 | Eyes Closed: Change at 8 hours post-dose | 0.92 units on a scale | Standard Deviation 2.969 |
| Treatment C: E2730 120 mg | 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 | Eye Closure: At Baseline | 9.20 units on a scale | Standard Deviation 3.114 |
| Treatment C: E2730 120 mg | 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 | Eyes Open: At Baseline | 7.00 units on a scale | Standard Deviation 2.646 |
Comparison: 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.90% CI: [-0.75, 1.54]
Comparison: 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.90% CI: [-0.6, 1.21]
Comparison: 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.90% CI: [-1.16, 4.39]
Comparison: 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.90% CI: [-0.89, 2.98]
Comparison: 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.90% CI: [-1.87, 2.28]
Comparison: 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.90% CI: [-0.57, 3.11]
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).
Time frame: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: Placebo | Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity | NA correlation coefficient |
| Treatment B: E2730 40 mg | Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity | NA correlation coefficient |
| Treatment C: E2730 120 mg | Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity | NA correlation coefficient |
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.
Time frame: First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71)
Population: The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Placebo | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Hematology | 0 Participants |
| Treatment A: Placebo | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Clinical Chemistry | 0 Participants |
| Treatment A: Placebo | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Liver Function Test | 0 Participants |
| Treatment B: E2730 40 mg | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Hematology | 0 Participants |
| Treatment B: E2730 40 mg | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Clinical Chemistry | 0 Participants |
| Treatment B: E2730 40 mg | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Liver Function Test | 0 Participants |
| Treatment C: E2730 120 mg | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Clinical Chemistry | 0 Participants |
| Treatment C: E2730 120 mg | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Liver Function Test | 0 Participants |
| Treatment C: E2730 120 mg | Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test | Hematology | 0 Participants |
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.
Time frame: First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71)
Population: The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Placebo | Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs | 0 Participants |
| Treatment B: E2730 40 mg | Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs | 0 Participants |
| Treatment C: E2730 120 mg | Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs | 0 Participants |
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.
Time frame: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Placebo | 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 | No Response | 4 Participants |
| Treatment A: Placebo | 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 | Partial Response | 1 Participants |
| Treatment A: Placebo | 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 | 0 Participants |
| Treatment B: E2730 40 mg | 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 | No Response | 4 Participants |
| Treatment B: E2730 40 mg | 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 | 0 Participants |
| Treatment B: E2730 40 mg | 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 | Partial Response | 0 Participants |
| Treatment C: E2730 120 mg | 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 | Partial Response | 0 Participants |
| Treatment C: E2730 120 mg | 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 | 0 Participants |
| Treatment C: E2730 120 mg | 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 | No Response | 5 Participants |
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.
Time frame: First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71)
Population: The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Treatment B: E2730 40 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Treatment C: E2730 120 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
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.
Time frame: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Placebo | 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 | Eyes Closed | NA hours |
| Treatment A: Placebo | 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 | Eye Closure | NA hours |
| Treatment A: Placebo | 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 | Eyes Opened | NA hours |
| Treatment B: E2730 40 mg | 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 | Eyes Closed | NA hours |
| Treatment B: E2730 40 mg | 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 | Eye Closure | NA hours |
| Treatment B: E2730 40 mg | 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 | Eyes Opened | NA hours |
| Treatment C: E2730 120 mg | 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 | Eye Closure | NA hours |
| Treatment C: E2730 120 mg | 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 | Eyes Opened | NA hours |
| Treatment C: E2730 120 mg | 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 | Eyes Closed | NA hours |
Secondary
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite
Time frame: Days 1, 22 and 43: 0-8 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: Placebo | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite | E2730 | 4.15 hours |
| Treatment A: Placebo | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite | N-acetyl metabolite | 1.65 hours |
| Treatment B: E2730 40 mg | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite | E2730 | 1.78 hours |
| Treatment B: E2730 40 mg | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite | N-acetyl metabolite | 4.00 hours |