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Safety Review
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo, E2082 2.5 mg, E2082 25 mg, E2082 40 mg | Experimental | Participants will receive a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 1 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 2 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between all the treatment periods. |
|
| E2082 2.5 mg, E2082 25 mg, Placebo, E2082 40 mg | Experimental | Participants will receive a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 1 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 2 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods. |
|
| E2082 25 mg, Placebo, E2082 2.5 mg, E2082 40 mg | Experimental | Participants will receive a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 1 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 2 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Participants will receive E2082-matched placebo tablets orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in the Photoparoxysmal Response (PPR) Range in the Most Sensitive Eye Condition at 8 Hours Postdose on Day 1 of Each Treatment Period | PPR was an electroencephalogram (EEG) trait of spike and spike-wave discharges in response to photic stimulation. Intermittent photic stimulation (IPS)-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 hertz (Hz). The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, standard photosensitivity response (SPR) was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. Most sensitive eye condition was defined as one that yielded the largest SPR before dosing. | Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trials, Inc. and Arkansas Epilepsy Program | Little Rock | Arkansas | 72205 | United States | ||
| Consultants in Epilepsy & Neurology, PLLC |
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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The study was terminated due to safety concerns from a phase 1 study (E2082-J081-001; NCT03402178) and preclinical animal toxicity testing.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Placebo + E2082 2.5 mg + E2082 25 mg + E2082 40 mg | Participants received, E2082-matched placebo (Treatment A) tablet, orally, once on Day 1 in Treatment Period 1, followed by E2082 2.5 milligram (mg) (Treatment B) tablet, orally, once on Day 1 in Treatment Period 2, followed by E2082 25 mg (Treatment C) tablet, orally, once on Day 1 in Treatment Period 3, followed by E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 4 (Open-label). A washout phase of at least 2 weeks was maintained between all the treatment periods. |
| FG001 | Sequence 2: E2082 2.5 mg + E2082 25 mg + Placebo + E2082 40 mg | Participants received, E2082 2.5 mg (Treatment B) tablet, orally, once on Day 1 in Treatment Period 1, followed by E2082 25 mg (Treatment C) tablet, orally, once on Day 1 in Treatment Period 2, followed by E2082-matched placebo (Treatment A) tablet, orally, once on Day 1 in Treatment Period 3, followed by E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 4 (Open-label). A washout phase of at least 2 weeks was maintained between the treatment periods. |
| FG002 | Sequence 3: E2082 25 mg + Placebo + E2082 2.5 mg + E2082 40 mg | Participants received, E2082 25 mg (Treatment C) tablet, orally, once on Day 1 in Treatment Period 1, followed by E2082-matched placebo (Treatment A) tablet, orally, once on Day 1 in Treatment Period 2, followed by E2082 2.5 mg (Treatment B) tablet, orally, once on Day 1 in Treatment Period 3, followed by E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 4 (Open-label). A washout phase of at least 2 weeks was maintained between the treatment periods. |
| FG003 | Sequence 4: Placebo + E2082 25 mg + E2082 2.5 mg + E2082 40 mg | Participants received, E2082-matched placebo (Treatment A) tablet, orally, once on Day 1 in Treatment Period 1, followed by E2082 25 mg (Treatment C) tablet, orally, once on Day 1 in Treatment Period 2, followed by E2082 2.5 mg (Treatment B) tablet, orally, once on Day 1 in Treatment Period 3, followed by E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 4 (Open-label). A washout phase of at least 2 weeks was maintained between the treatment periods. |
| FG004 | Sequence 5: E2082 2.5 mg + Placebo + E2082 25 mg + E2082 40 mg | Participants received, E2082 2.5 mg (Treatment B) tablet, orally, once on Day 1 in Treatment Period 1, followed by E2082-matched placebo (Treatment A) tablet, orally, once on Day 1 in Treatment Period 2, followed by E2082 25 mg (Treatment C) tablet, orally, once on Day 1 in Treatment Period 3, followed by E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 4 (Open-label). A washout phase of at least 2 weeks was maintained between the treatment periods. |
| FG005 | Sequence 6: E2082 25 mg + E2082 2.5 mg + Placebo + E2082 40 mg | Participants received, E2082 25 mg (Treatment C) tablet, orally, once on Day 1 in Treatment Period 1, followed by E2082 2.5 mg (Treatment B) tablet, orally, once on Day 1 in Treatment Period 2, followed by E2082-matched placebo (Treatment A) tablet, orally, once on Day 1 in Treatment Period 3, followed by E2082 40 mg tablet, orally, once on Day 1 in Treatment Period 4 (Open-label). A washout phase of at least 2 weeks was maintained between the treatment periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (1 Day) |
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| Washout Phase (at Least 2 Weeks) |
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| Treatment Period 2 (1 Day) |
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| Washout Phase (at Least 2 Weeks) |
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| Treatment Period 3 (1 Day) |
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| Washout Phase (at Least 2 Weeks) |
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| Treatment Period 4 (1 Day) |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change From Baseline in the 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period |
Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A: Placebo | Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye movement disorder | Eye disorders | MedDRA 22.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
The study was terminated due to safety concerns from a phase 1 study (E2082-J081-001; NCT03402178) and preclinical animal toxicity testing.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | +1-888-274-2378 | esi_medinfo@eisai.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 12, 2019 | Jun 17, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 4, 2019 | Jun 17, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020195 | Epilepsy, Reflex |
| D004827 | Epilepsy |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
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The study consists of a crossover design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
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The study consists of a randomized double-blind design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4.
| Placebo, E2082 25 mg, E2082 2.5 mg, E2082 40 mg | Experimental | Participants will receive a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 1 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 2 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods. |
|
| E2082 2.5 mg, Placebo, E2082 25 mg, E2082 40 mg | Experimental | Participants will receive a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 1 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 2 followed by a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods. |
|
| E2082 25 mg, E2082 2.5 mg, Placebo, E2082 40 mg | Experimental | Participants will receive a single dose of E2082 tablets at 25 mg orally (Treatment C) in Treatment Period 1 followed by a single dose of E2082 tablets at 2.5 mg orally (Treatment B) in Treatment Period 2 followed by a single dose of E2082-matched placebo tablet orally (Treatment A) in Treatment Period 3 followed by a single dose of E2082 tablets at 40 mg orally in Treatment Period 4. A wash-out phase of at least 2 weeks will be maintained between the treatment periods. |
|
| E2082 | Drug | Participants will receive E2082 tablets orally. |
|
| Baseline (30 minutes-2 hours) and at 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) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Time to onset of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean Response of standardized photosensitivity response (SPR) across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially intermittent photosensitivity (intermittent photic stimulation [IPS]) assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz. | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
| Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) were reported. PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
| Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. Duration of mean suppression was defined as the difference in hours between the onset of mean suppression and the end of mean suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants was at least 3 units below the mean SPR at baseline. The end of mean suppression was defined as the last time (second time) with two successive reductions in mean SPR across participants of at least 3 units lower than the mean SPR at baseline. Photosensitivity response were essentially IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz. | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
| Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Complete suppression, reduction (partial response), and no change (no response) of PPR will be measured. Complete suppression was defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response was defined as a reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response was defined as not meeting complete suppression or partial suppression definitions. | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
| Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | BL-VAS system was used to assess the extent of damage to the extrapyramidal system and the motor functions that it controls. The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 millimeter (mm) about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three subscales: a.) Anxiety, b.) Dysphoria, c.) sedation with each item ranges from 0 to 100 and higher scores indicated better condition. | Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment period |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) |
| 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 |
| Boise |
| Idaho |
| 83702 |
| United States |
| Johns Hopkins University- School of Medicine | Baltimore | Maryland | 21287 | United States |
| Washington University Hospital | St Louis | Missouri | 63110 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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|
| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period |
|
|
|
| Secondary | Time to Onset of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Time to onset of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean Response of standardized photosensitivity response (SPR) across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially intermittent photosensitivity (intermittent photic stimulation [IPS]) assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz. | 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. | Posted | Number | hours | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
|
|
|
| Secondary | Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) were reported. PPR was an EEG trait of spike and spike-wave discharges in response to photic stimulation. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open) at ascending and then descending photo stimulation administered at 14 standard frequencies: 2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50, and 60 Hz. The lower and upper limit of photosensitivity to IPS threshold frequency were determined for each eye condition. From this range, SPR was derived. SPR is an integer score that ranges from 0 to 14, with lower scores representing better outcomes. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
|
|
|
| Secondary | Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean and mean change from baseline SPR data across participants. Duration of mean suppression was defined as the difference in hours between the onset of mean suppression and the end of mean suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants was at least 3 units below the mean SPR at baseline. The end of mean suppression was defined as the last time (second time) with two successive reductions in mean SPR across participants of at least 3 units lower than the mean SPR at baseline. Photosensitivity response were essentially IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz. | 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. | Posted | Number | hours | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
|
|
|
| Secondary | Number of Participants With Complete Suppression, Partial Response, and no Response of Standardized Photosensitivity Response (SPR) up to 8 Hours Postdose on Day 1 of Each Treatment Period | Complete suppression, reduction (partial response), and no change (no response) of PPR will be measured. Complete suppression was defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response was defined as a reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response was defined as not meeting complete suppression or partial suppression definitions. | 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. | Posted | Count of Participants | Participants | Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment period |
|
|
|
| Secondary | Change From Baseline in Bond and Lader Visual Analogue Scales (BL-VAS) at 1, 2, 4, 6, and 8 Hours Post-dose in Each Treatment Period | BL-VAS system was used to assess the extent of damage to the extrapyramidal system and the motor functions that it controls. The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 millimeter (mm) about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three subscales: a.) Anxiety, b.) Dysphoria, c.) sedation with each item ranges from 0 to 100 and higher scores indicated better condition. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment period |
|
|
|
| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | 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. | Posted | Count of Participants | Participants | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 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. | Posted | Count of Participants | Participants | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) |
|
|
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| Secondary | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 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. | Posted | Count of Participants | Participants | Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71) |
|
|
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| Secondary | Cmax: Maximum Observed Plasma Concentration for E2082 | 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. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period |
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| Secondary | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082 | 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. | Posted | Median | Full Range | hour | Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period |
|
|
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| Secondary | AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2082 | 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. | Posted | Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment period |
|
|
|
| 0 |
| 5 |
| 1 |
| 5 |
| 2 |
| 5 |
| EG001 | Treatment B: E2082 2.5 mg | Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. | 0 | 5 | 0 | 5 | 2 | 5 |
| EG002 | Treatment C: E2082 25 mg | Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG003 | Open-label Treatment: E2082 40 mg | Participants received, E2082 40 mg tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences. | 0 | 4 | 0 | 4 | 2 | 4 |
| Disturbance in attention | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Aggression | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
|
| Anger | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
Not provided
Not provided
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Eye Closure: Change at 8 hours postdose |
|
| Eyes Closed: Baseline |
|
| Eyes Closed: Change at 8 hours postdose |
|
| Eyes Open: Baseline |
|
| Eyes Open: Change at 8 hours postdose |
|
| Eyes Closed |
|
| Eyes Opened |
|
| Eye Closure: Maximum Change |
|
| Eyes Closed: Baseline |
|
| Eyes Closed: Maximum Change |
|
| Eyes Opened: Baseline |
|
| Eyes Opened: Maximum Change |
|
| Eyes Closed: Duration |
|
| Eyes Opened: Duration |
|
| Partial Response |
|
| No Response |
|
| Anxiety: Change at 1 hour post-dose |
|
| Anxiety: Change at 2 hours post-dose |
|
| Anxiety: Change at 4 hours post-dose |
|
| Anxiety: Change at 6 hours post-dose |
|
| Anxiety: Change at 8 hours post-dose |
|
| Dysphoria: Baseline |
|
| Dysphoria: Change at 1 hour post-dose |
|
| Dysphoria: Change at 2 hours post-dose |
|
| Dysphoria: Change at 4 hours post-dose |
|
| Dysphoria: Change at 6 hours post-dose |
|
| Dysphoria: Change at 8 hours post-dose |
|
| Sedation: Baseline |
|
| Sedation: Change at 1 hour post-dose |
|
| Sedation: Change at 2 hours post-dose |
|
| Sedation: Change at 4 hours post-dose |
|
| Sedation: Change at 6 hours post-dose |
|
| Sedation: Change at 8 hours post-dose |
|