Photosensitive Epilepsy
Conditions
Keywords
E2082, Epilepsy, Photosensitive, Anti-epileptic, Seizures, Photoparoxysmal response, PPR
Brief summary
The primary purpose of the study is to assess pharmacodynamic (PD) activity of E2082 as measured by suppression of epileptic photoparoxysmal response (PPR) in the participant's most sensitive eye condition in participants with photosensitive epilepsy, compared to placebo.
Interventions
DRUGPlacebo
Participants will receive E2082-matched placebo tablets orally.
DRUGE2082
Participants will receive E2082 tablets orally.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study consists of a randomized double-blind design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
Intervention model description
The study consists of a crossover design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis and/or history of a PPR on EEG. 2. If currently being treated with antiepileptic drug (AED), up to a maximum of 3 concomitant AEDs is allowed provided that doses must have remained stable for at least 4 weeks (or at least 8 weeks if recently initiated) before screening. 3. Reproducible IPS-induced PPR on EEG of at least 3 points on the SPR scale in at least 1 eye condition (eye closure, eyes closed, eyes open) on at least 3 of the EEGs performed at screening. 4. Body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m\^2) (inclusive) and a total body weight greater than or equal to (\>=) 45 kilogram (kg) at screening. 5. Agrees to refrain from strenuous exercise and alcohol consumption during the 24-hour period before screening and before each treatment day.
Exclusion criteria
1. Females who are breastfeeding or pregnant at screening or baseline. 2. Male participants who have not had a successful vasectomy, they and their female partners not of childbearing potential, or practicing highly effective contraception throughout the study period and for 28 days after study drug discontinuation. No sperm donation is allowed during the study period and for 28 days after study drug discontinuation. 3. History of nonepileptic seizures (example, metabolic, structural, or pseudoseizures) while on any antiepileptic medication. 4. History of status epilepticus while on any antiepileptic medication(s) within 2 years before screening. 5. Ongoing or history of generalized tonic-clonic seizures (GTCS) within 6 months before screening. 6. Participants who had developed a clinical seizure during previous PPR assessment, or who experiences a clinical seizure during the Screening IPS procedure. 7. Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (example, increase in spike-wave activity) at screening. 8. Inability to follow restriction on watching television, or use of any device(s) with an animated screen (example, computer, video games, tablets, or smart phone) from the time of arrival at the study center until study procedures are completed for that day. 9. Use of perampanel within 6 weeks before screening. 10. Use of felbamate for less than 2 years or where the dose has not been stable for at least 8 weeks before Visit 1. 11. Use of vigabatrin within 5 months before screening and/or documented evidence of vigabatrin associated clinically significant abnormality in a visual perimetry test. 12. Use of benzodiazepines for non-epilepsy related indications. Intermittent use of benzodiazepines as rescue medication or stable dosage (greater than 4 weeks before screening) for epilepsy indications is allowed. 13. Concomitant use of cannabinoids. 14. Use of concomitant potent cytochrome P450 (CYP)3A inducers or inhibitors within 4 weeks or 5 half-lives, whichever is longer. 15. Vagus nerve stimulation (VNS) implanted within 5 months or changes in parameter within 4 weeks before screening. 16. On a ketogenic diet for which the diet is not a stable regimen for at least 4 weeks before screening. 17. Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 18. A history of prolonged QT syndrome or risk factors for torsade de pointes, or the use of concomitant medications that cause QT prolongation as demonstrated on screening electrocardiogram (ECG). 19. Any suicidal ideation with intent with or without a plan within 6 months before or during screening, and/or any lifetime suicidal behavior. 20. Any psychotic disorder(s) or unstable recurrent affective disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period | PPR was an electroencephalogram (EEG) trait of spike and spike-wave discharges in response to photic stimulation. Intermittent photic stimulation (IPS)-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 hertz (Hz). The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, standard photosensitivity response (SPR) was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. Most sensitive eye condition was defined as one that yielded the largest SPR before dosing. |
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 Postdose on Day 1 of Each Treatment Period | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period | Time to onset of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean Response of standardized photosensitivity response (SPR) across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially intermittent photosensitivity (intermittent photic stimulation \[IPS\]) assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz. |
| Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period | Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) were reported. PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. |
| Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period | Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. Duration of mean suppression was defined as the difference in hours between the onset of mean suppression and the end of mean suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants was at least 3 units below the mean SPR at baseline. The end of mean suppression was defined as the last time (second time) with two successive reductions in mean SPR across participants of at least 3 units lower than the mean SPR at baseline. Photosensitivity response were essentially IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz. |
| Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period | Complete suppression, reduction (partial response), and no change (no response) of PPR will be measured. Complete suppression was defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response was defined as a reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response was defined as not meeting complete suppression or partial suppression definitions. |
| Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment period | BL-VAS system was used to assess the extent of damage to the extrapyramidal system and the motor functions that it controls. The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 millimeter (mm) about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three subscales: a.) Anxiety, b.) Dysphoria, c.) sedation with each item ranges from 0 to 100 and higher scores indicated better condition. |
| Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period | PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) | — |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) | — |
| Cmax: Maximum Observed Plasma Concentration for E2082 | Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period | — |
| Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082 | Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period | — |
| AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082 | Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in the United States from 31 October 2018 to 18 June 2019. A total of 8 participants were screened and enrolled, of which 5 participants were randomized and treated, of which, 4 participants completed both crossover and open label treatments in the study.
Pre-assignment details
The study was terminated due to safety concerns from a phase 1 study (E2082-J081-001; NCT03402178) and preclinical animal toxicity testing.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants Participants received E2082-matched placebo (Treatment A) or E2082 2.5 mg (Treatment B) or E2082 25 mg (Treatment C) and E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 1 to 4 as per assigned treatment sequence. A washout phase of at least 2 weeks was maintained between all the treatment periods. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 2 (1 Day) | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Customized <=18 years | 0 Participants |
| Age, Customized >=60 years | 0 Participants |
| Age, Customized Between 18 and 60 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 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 | 5 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 2 / 5 | 2 / 5 | 1 / 4 | 2 / 4 |
| serious Total, serious adverse events | 1 / 5 | 0 / 5 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period
PPR was an electroencephalogram (EEG) trait of spike and spike-wave discharges in response to photic stimulation. Intermittent photic stimulation (IPS)-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 hertz (Hz). The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, standard photosensitivity response (SPR) was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. Most sensitive eye condition was defined as one that yielded the largest SPR before dosing.
Time frame: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period
Population: The pharmacodynamic (PD) analysis set was the group of randomized participants who received at least 1 dose of study drug and have 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 Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Change at 8 hours postdose | 0.00 units on a scale | Standard Deviation 1.517 |
| Treatment A: Placebo | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline | 6.80 units on a scale | Standard Deviation 4.604 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline | 5.60 units on a scale | Standard Deviation 4.336 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Change at 8 hours postdose | 1.16 units on a scale | Standard Deviation 1.381 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline | 6.00 units on a scale | Standard Deviation 3.651 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Change at 8 hours postdose | -3.90 units on a scale | Standard Deviation 2.928 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Change at 8 hours postdose | -5.25 units on a scale | Standard Deviation 0.957 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | Baseline | 6.50 units on a scale | Standard Deviation 1.732 |
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. Least Square (LS) Mean Difference was calculated for 2.5 mg versus (vs) Placebo only.90% CI: [-0.98, 3.22]
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. LS Mean Difference was calculated for 25 mg vs Placebo only.90% CI: [-6.35, -1.99]
Secondary
AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082
Time frame: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
Population: The PK analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PK data to derive at least 1 PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082 | 633 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 142 |
| Treatment B: E2082 2.5 mg | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082 | 3990 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 344 |
| Treatment C: E2082 25 mg | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082 | 5750 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 787 |
Secondary
Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period
BL-VAS system was used to assess the extent of damage to the extrapyramidal system and the motor functions that it controls. The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 millimeter (mm) about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three subscales: a.) Anxiety, b.) Dysphoria, c.) sedation with each item ranges from 0 to 100 and higher scores indicated better condition.
Time frame: Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment period
Population: The PD analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PD data to derive at least 1 PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 2 hours post-dose | 9.44 score on a scale | Standard Deviation 9.06 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 1 hour post-dose | 4.36 score on a scale | Standard Deviation 5.963 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 4 hours post-dose | -0.26 score on a scale | Standard Deviation 1.137 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Baseline | 28.90 score on a scale | Standard Deviation 18.748 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Baseline | 29.42 score on a scale | Standard Deviation 22.731 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 4 hours post-dose | 2.82 score on a scale | Standard Deviation 8.885 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 2 hours post-dose | 2.84 score on a scale | Standard Deviation 8.996 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 8 hours post-dose | 1.08 score on a scale | Standard Deviation 3.976 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 6 hours post-dose | -0.72 score on a scale | Standard Deviation 3.883 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 8 hours post-dose | 0.30 score on a scale | Standard Deviation 6.288 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 1 hour post-dose | -4.44 score on a scale | Standard Deviation 7.134 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 6 hours post-dose | 0.58 score on a scale | Standard Deviation 2.567 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 8 hours post-dose | -0.72 score on a scale | Standard Deviation 3.935 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 4 hours post-dose | 5.50 score on a scale | Standard Deviation 5.247 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Baseline | 33.58 score on a scale | Standard Deviation 23.032 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 1 hour post-dose | -7.36 score on a scale | Standard Deviation 23.099 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 6 hours post-dose | -0.88 score on a scale | Standard Deviation 3.397 |
| Treatment A: Placebo | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 2 hours post-dose | 1.80 score on a scale | Standard Deviation 3.616 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Baseline | 29.42 score on a scale | Standard Deviation 22.731 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 8 hours post-dose | 0.50 score on a scale | Standard Deviation 6.615 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Baseline | 28.90 score on a scale | Standard Deviation 18.748 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 4 hours post-dose | -1.94 score on a scale | Standard Deviation 3.889 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 6 hours post-dose | 1.56 score on a scale | Standard Deviation 3.591 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 2 hours post-dose | -10.04 score on a scale | Standard Deviation 20.028 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 1 hour post-dose | -9.44 score on a scale | Standard Deviation 19.55 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 8 hours post-dose | -2.36 score on a scale | Standard Deviation 3.965 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Baseline | 33.58 score on a scale | Standard Deviation 23.032 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 4 hours post-dose | -8.96 score on a scale | Standard Deviation 18.512 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 2 hours post-dose | -1.62 score on a scale | Standard Deviation 2.909 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 1 hour post-dose | 6.20 score on a scale | Standard Deviation 4.933 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 2 hours post-dose | 7.23 score on a scale | Standard Deviation 7.032 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 6 hours post-dose | -9.70 score on a scale | Standard Deviation 21.895 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 6 hours post-dose | 2.70 score on a scale | Standard Deviation 9.281 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 8 hours post-dose | 5.92 score on a scale | Standard Deviation 43.792 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 1 hour post-dose | -0.50 score on a scale | Standard Deviation 6.536 |
| Treatment B: E2082 2.5 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 4 hours post-dose | 2.84 score on a scale | Standard Deviation 6.993 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Baseline | 24.33 score on a scale | Standard Deviation 22.712 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 8 hours post-dose | 18.78 score on a scale | Standard Deviation 35.818 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Baseline | 36.23 score on a scale | Standard Deviation 25.703 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 6 hours post-dose | 2.30 score on a scale | Standard Deviation 3.866 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 8 hours post-dose | -0.30 score on a scale | Standard Deviation 1.137 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Baseline | 31.90 score on a scale | Standard Deviation 20.215 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 4 hours post-dose | 0.10 score on a scale | Standard Deviation 1.01 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 6 hours post-dose | -0.87 score on a scale | Standard Deviation 2.766 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 1 hour post-dose | 0.50 score on a scale | Standard Deviation 0.883 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 2 hours post-dose | 2.68 score on a scale | Standard Deviation 3.886 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 4 hours post-dose | 2.47 score on a scale | Standard Deviation 3.661 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 1 hour post-dose | 6.45 score on a scale | Standard Deviation 3.724 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 2 hours post-dose | 7.40 score on a scale | Standard Deviation 4.291 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 6 hours post-dose | 7.08 score on a scale | Standard Deviation 4.424 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 4 hours post-dose | 11.55 score on a scale | Standard Deviation 9.627 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 2 hours post-dose | -1.05 score on a scale | Standard Deviation 2.684 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 1 hour post-dose | -0.37 score on a scale | Standard Deviation 0.386 |
| Treatment C: E2082 25 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 8 hours post-dose | 2.38 score on a scale | Standard Deviation 3.256 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 1 hour post-dose | -2.40 score on a scale | Standard Deviation 3.382 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Baseline | 36.23 score on a scale | Standard Deviation 25.703 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 4 hours post-dose | 6.08 score on a scale | Standard Deviation 4.219 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 6 hours post-dose | -0.42 score on a scale | Standard Deviation 4.452 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 6 hours post-dose | 10.30 score on a scale | Standard Deviation 12.258 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 4 hours post-dose | -0.10 score on a scale | Standard Deviation 4.017 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 2 hours post-dose | 19.73 score on a scale | Standard Deviation 42.748 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Baseline | 31.90 score on a scale | Standard Deviation 20.215 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Change at 8 hours post-dose | -0.85 score on a scale | Standard Deviation 3.171 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Anxiety: Baseline | 24.33 score on a scale | Standard Deviation 22.712 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 8 hours post-dose | -0.40 score on a scale | Standard Deviation 1.337 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 1 hour post-dose | 5.98 score on a scale | Standard Deviation 4.131 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 4 hours post-dose | 2.55 score on a scale | Standard Deviation 3.486 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 6 hours post-dose | 0.02 score on a scale | Standard Deviation 2.334 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 8 hours post-dose | 9.53 score on a scale | Standard Deviation 9.466 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 2 hours post-dose | 3.30 score on a scale | Standard Deviation 3.503 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Sedation: Change at 2 hours post-dose | 8.18 score on a scale | Standard Deviation 5.702 |
| Open-label Treatment: E2082 40 mg | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | Dysphoria: Change at 1 hour post-dose | 2.28 score on a scale | Standard Deviation 4.11 |
Secondary
Cmax: Maximum Observed Plasma Concentration for E2082
Time frame: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
Population: The pharmacokinetic (PK) analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PK data to derive at least 1 PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Placebo | Cmax: Maximum Observed Plasma Concentration for E2082 | 100 nanogram per milliliter (ng/mL) | Standard Deviation 25.1 |
| Treatment B: E2082 2.5 mg | Cmax: Maximum Observed Plasma Concentration for E2082 | 617 nanogram per milliliter (ng/mL) | Standard Deviation 30.3 |
| Treatment C: E2082 25 mg | Cmax: Maximum Observed Plasma Concentration for E2082 | 851 nanogram per milliliter (ng/mL) | Standard Deviation 91.8 |
Secondary
Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period
Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. Duration of mean suppression was defined as the difference in hours between the onset of mean suppression and the end of mean suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants was at least 3 units below the mean SPR at baseline. The end of mean suppression was defined as the last time (second time) with two successive reductions in mean SPR across participants of at least 3 units lower than the mean SPR at baseline. Photosensitivity response were essentially IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz.
Time frame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Population: The PD analysis set was the group of randomized participants who received at least 1 dose of study drug and have 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 Postdose 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Duration | NA hours |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Duration | NA hours |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Duration | NA hours |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Duration | NA hours |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Duration | 7 hours |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Duration | 7 hours |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Duration | 7 hours |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Duration | 7 hours |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Duration | 7 hours |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Duration | 7 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 Postdose on Day 1 of Each Treatment Period
Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) were reported. PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes.
Time frame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Population: The PD analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PD data to derive at least 1 PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Maximum Change | 1.80 units on a scale | Standard Deviation 2.588 |
| 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 5.40 units on a scale | Standard Deviation 4.722 |
| 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Maximum Change | 2.00 units on a scale | Standard Deviation 3.24 |
| 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Baseline | 5.20 units on a scale | Standard Deviation 5.404 |
| 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Maximum Change | 1.40 units on a scale | Standard Deviation 3.912 |
| 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 6.20 units on a scale | Standard Deviation 4.087 |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 6.00 units on a scale | Standard Deviation 3.873 |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Maximum Change | 1.80 units on a scale | Standard Deviation 2.588 |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 5.60 units on a scale | Standard Deviation 4.722 |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Maximum Change | 2.00 units on a scale | Standard Deviation 2.345 |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Baseline | 4.60 units on a scale | Standard Deviation 4.037 |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Maximum Change | 1.80 units on a scale | Standard Deviation 3.633 |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Maximum Change | -4.50 units on a scale | Standard Deviation 3.697 |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Maximum Change | -4.25 units on a scale | Standard Deviation 2.63 |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Maximum Change | -4.25 units on a scale | Standard Deviation 3.304 |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Baseline | 5.00 units on a scale | Standard Deviation 3.83 |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 5.75 units on a scale | Standard Deviation 4.646 |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 5.25 units on a scale | Standard Deviation 3.202 |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 6.25 units on a scale | Standard Deviation 2.872 |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Maximum Change | -6.25 units on a scale | Standard Deviation 4.646 |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened: Baseline | 6.25 units on a scale | Standard Deviation 4.646 |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed: Maximum Change | -6.25 units on a scale | Standard Deviation 2.872 |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 5.50 units on a scale | Standard Deviation 2.887 |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eye Closure: Maximum Change | -5.25 units on a scale | Standard Deviation 2.5 |
Secondary
Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period
PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes.
Time frame: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period
Population: The PD analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PD data to derive at least 1 PD parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Placebo | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 6.2 units on a scale | Standard Deviation 4.09 |
| Treatment A: Placebo | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Change at 8 hours postdose | 0.6 units on a scale | Standard Deviation 1.66 |
| Treatment A: Placebo | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 5.4 units on a scale | Standard Deviation 4.72 |
| Treatment A: Placebo | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Change at 8 hours postdose | 1.1 units on a scale | Standard Deviation 1.4 |
| Treatment A: Placebo | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Baseline | 5.2 units on a scale | Standard Deviation 5.4 |
| Treatment A: Placebo | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Change at 8 hours postdose | 0.5 units on a scale | Standard Deviation 2.18 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Change at 8 hours postdose | 0.8 units on a scale | Standard Deviation 1.12 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Change at 8 hours postdose | 0.7 units on a scale | Standard Deviation 1.56 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 6 units on a scale | Standard Deviation 3.87 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 5.6 units on a scale | Standard Deviation 4.72 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Change at 8 hours postdose | 0.4 units on a scale | Standard Deviation 0.91 |
| Treatment B: E2082 2.5 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Baseline | 4.6 units on a scale | Standard Deviation 4.04 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Change at 8 hours postdose | -3.7 units on a scale | Standard Deviation 3.93 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 5.3 units on a scale | Standard Deviation 3.2 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Change at 8 hours postdose | -3.7 units on a scale | Standard Deviation 2.96 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Change at 8 hours postdose | -3.9 units on a scale | Standard Deviation 3.28 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Baseline | 5 units on a scale | Standard Deviation 3.83 |
| Treatment C: E2082 25 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 5.8 units on a scale | Standard Deviation 4.65 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Baseline | 6.3 units on a scale | Standard Deviation 4.65 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Open: Change at 8 hours postdose | -5.8 units on a scale | Standard Deviation 4.09 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Change at 8 hours postdose | -4.3 units on a scale | Standard Deviation 1.71 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Change at 8 hours postdose | -5.4 units on a scale | Standard Deviation 1.62 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eye Closure: Baseline | 5.5 units on a scale | Standard Deviation 2.89 |
| Open-label Treatment: E2082 40 mg | Mean Change From Baseline in PPR Ranges in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Postdose on Day 1 of Each Treatment Period | Eyes Closed: Baseline | 6.3 units on a scale | Standard Deviation 2.87 |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Time frame: Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug and have at least 1 postdose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Placebo | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Treatment B: E2082 2.5 mg | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Treatment C: E2082 25 mg | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Open-label Treatment: E2082 40 mg | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug and have at least 1 postdose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Placebo | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Treatment B: E2082 2.5 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Treatment C: E2082 25 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Open-label Treatment: E2082 40 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period
Complete suppression, reduction (partial response), and no change (no response) of PPR will be measured. Complete suppression was defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response was defined as a reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response was defined as not meeting complete suppression or partial suppression definitions.
Time frame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Population: The PD analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PD data to derive at least 1 PD parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Placebo | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Complete Suppression | 0 Participants |
| Treatment A: Placebo | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | No Response | 5 Participants |
| Treatment A: Placebo | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Partial Response | 0 Participants |
| Treatment B: E2082 2.5 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Complete Suppression | 0 Participants |
| Treatment B: E2082 2.5 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | No Response | 5 Participants |
| Treatment B: E2082 2.5 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Partial Response | 0 Participants |
| Treatment C: E2082 25 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Partial Response | 0 Participants |
| Treatment C: E2082 25 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Complete Suppression | 2 Participants |
| Treatment C: E2082 25 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | No Response | 2 Participants |
| Open-label Treatment: E2082 40 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Complete Suppression | 2 Participants |
| Open-label Treatment: E2082 40 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | No Response | 0 Participants |
| Open-label Treatment: E2082 40 mg | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Partial Response | 2 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug and have at least 1 postdose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Treatment B: E2082 2.5 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Treatment C: E2082 25 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| Open-label Treatment: E2082 40 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 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 Postdose on Day 1 of Each Treatment Period
Time to onset of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean Response of standardized photosensitivity response (SPR) across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially intermittent photosensitivity (intermittent photic stimulation \[IPS\]) assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz.
Time frame: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period
Population: The PD analysis set was the group of randomized participants who received at least 1 dose of study drug and have 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 Postdose 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened | 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 Postdose on Day 1 of Each Treatment Period | Eye Closure | NA hours |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed | NA hours |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eye Closure | NA hours |
| Treatment B: E2082 2.5 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened | NA hours |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed | 1 hours |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened | 1 hours |
| Treatment C: E2082 25 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 Postdose on Day 1 of Each Treatment Period | Eye Closure | 1 hours |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Closed | 1 hours |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eye Closure | 1 hours |
| Open-label Treatment: E2082 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 Postdose on Day 1 of Each Treatment Period | Eyes Opened | 1 hours |
Secondary
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082
Time frame: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period
Population: The PK analysis set was the group of randomized participants who received at least 1 dose of study drug and have sufficient PK data to derive at least 1 PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Placebo | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082 | 3.93 hour |
| Treatment B: E2082 2.5 mg | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082 | 3.96 hour |
| Treatment C: E2082 25 mg | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082 | 3.99 hour |