Trial Outcomes & Findings for A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy (NCT NCT03686033)
NCT ID: NCT03686033
Last Updated: 2020-09-28
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
8 participants
Primary outcome timeframe
Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment period
Results posted on
2020-09-28
Participant Flow
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.
The study was terminated due to safety concerns from a phase 1 study (E2082-J081-001; NCT03402178) and preclinical animal toxicity testing.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (1 Day)
STARTED
|
1
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1
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1
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1
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1
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0
|
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Treatment Period 1 (1 Day)
COMPLETED
|
1
|
1
|
1
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1
|
1
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0
|
|
Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Phase (at Least 2 Weeks)
STARTED
|
1
|
1
|
1
|
1
|
0
|
0
|
|
Washout Phase (at Least 2 Weeks)
COMPLETED
|
1
|
1
|
1
|
1
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0
|
0
|
|
Washout Phase (at Least 2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
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0
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0
|
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Treatment Period 2 (1 Day)
STARTED
|
1
|
1
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1
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1
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1
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0
|
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Treatment Period 2 (1 Day)
COMPLETED
|
1
|
1
|
1
|
1
|
0
|
0
|
|
Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
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0
|
1
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0
|
|
Treatment Period 3 (1 Day)
STARTED
|
1
|
1
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1
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1
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0
|
0
|
|
Treatment Period 3 (1 Day)
COMPLETED
|
1
|
1
|
1
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1
|
0
|
0
|
|
Treatment Period 3 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 4 (1 Day)
STARTED
|
1
|
1
|
1
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1
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0
|
0
|
|
Treatment Period 4 (1 Day)
COMPLETED
|
1
|
1
|
1
|
1
|
0
|
0
|
|
Treatment Period 4 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Treatment Period 2 (1 Day)
Adverse Event
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy
Baseline characteristics by cohort
| Measure |
Overall Participants
n=5 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.
|
|---|---|
|
Age, Customized
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Customized
Between 18 and 60 years
|
5 Participants
n=5 Participants
|
|
Age, Customized
>=60 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
|
5.60 units on a scale
Standard Deviation 4.336
|
6.00 units on a scale
Standard Deviation 3.651
|
6.50 units on a scale
Standard Deviation 1.732
|
|
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
|
1.16 units on a scale
Standard Deviation 1.381
|
-3.90 units on a scale
Standard Deviation 2.928
|
-5.25 units on a scale
Standard Deviation 0.957
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) and at 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
|
6 units on a scale
Standard Deviation 3.87
|
5.8 units on a scale
Standard Deviation 4.65
|
5.5 units on a scale
Standard Deviation 2.89
|
|
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
|
0.4 units on a scale
Standard Deviation 0.91
|
-3.7 units on a scale
Standard Deviation 3.93
|
-4.3 units on a scale
Standard Deviation 1.71
|
|
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
|
5.6 units on a scale
Standard Deviation 4.72
|
5.3 units on a scale
Standard Deviation 3.2
|
6.3 units on a scale
Standard Deviation 2.87
|
|
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
|
0.7 units on a scale
Standard Deviation 1.56
|
-3.7 units on a scale
Standard Deviation 2.96
|
-5.4 units on a scale
Standard Deviation 1.62
|
|
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
|
4.6 units on a scale
Standard Deviation 4.04
|
5 units on a scale
Standard Deviation 3.83
|
6.3 units on a scale
Standard Deviation 4.65
|
|
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
|
0.8 units on a scale
Standard Deviation 1.12
|
-3.9 units on a scale
Standard Deviation 3.28
|
-5.8 units on a scale
Standard Deviation 4.09
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
Time to onset of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
NA hours
Time to onset of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
1 hours
|
1 hours
|
|
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
Time to onset of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
NA hours
Time to onset of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
1 hours
|
1 hours
|
|
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
Time to onset of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
NA hours
Time to onset of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
1 hours
|
1 hours
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
|
6.00 units on a scale
Standard Deviation 3.873
|
5.75 units on a scale
Standard Deviation 4.646
|
5.50 units on a scale
Standard Deviation 2.887
|
|
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
|
1.80 units on a scale
Standard Deviation 2.588
|
-4.50 units on a scale
Standard Deviation 3.697
|
-5.25 units on a scale
Standard Deviation 2.500
|
|
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
|
5.60 units on a scale
Standard Deviation 4.722
|
5.25 units on a scale
Standard Deviation 3.202
|
6.25 units on a scale
Standard Deviation 2.872
|
|
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
|
2.00 units on a scale
Standard Deviation 2.345
|
-4.25 units on a scale
Standard Deviation 2.630
|
-6.25 units on a scale
Standard Deviation 2.872
|
|
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
|
4.60 units on a scale
Standard Deviation 4.037
|
5.00 units on a scale
Standard Deviation 3.830
|
6.25 units on a scale
Standard Deviation 4.646
|
|
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 3.240
|
1.80 units on a scale
Standard Deviation 3.633
|
-4.25 units on a scale
Standard Deviation 3.304
|
-6.25 units on a scale
Standard Deviation 4.646
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
Duration of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
NA hours
Duration of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
7 hours
|
7 hours
|
|
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
Duration of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
NA hours
Duration of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
7 hours
|
7 hours
|
|
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
Duration of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
NA hours
Duration of suppression cannot be determined because no suppression of photosensitivity by at least 3 units below the mean SPR at baseline was observed throughout the 8-hour assessment period on each day of treatment.
|
7 hours
|
7 hours
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) up to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
|
0 Participants
|
2 Participants
|
2 Participants
|
|
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
|
0 Participants
|
0 Participants
|
2 Participants
|
|
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
|
5 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) and at 1,2,4,6 and 8 hours post-dose in each treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
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
|
29.42 score on a scale
Standard Deviation 22.731
|
24.33 score on a scale
Standard Deviation 22.712
|
24.33 score on a scale
Standard Deviation 22.712
|
|
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
|
-9.44 score on a scale
Standard Deviation 19.550
|
-0.37 score on a scale
Standard Deviation 0.386
|
-2.40 score on a scale
Standard Deviation 3.382
|
|
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
|
-10.04 score on a scale
Standard Deviation 20.028
|
-1.05 score on a scale
Standard Deviation 2.684
|
19.73 score on a scale
Standard Deviation 42.748
|
|
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
|
-8.96 score on a scale
Standard Deviation 18.512
|
0.10 score on a scale
Standard Deviation 1.010
|
-0.10 score on a scale
Standard Deviation 4.017
|
|
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
|
-9.70 score on a scale
Standard Deviation 21.895
|
-0.87 score on a scale
Standard Deviation 2.766
|
-0.42 score on a scale
Standard Deviation 4.452
|
|
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
|
5.92 score on a scale
Standard Deviation 43.792
|
18.78 score on a scale
Standard Deviation 35.818
|
-0.85 score on a scale
Standard Deviation 3.171
|
|
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
|
33.58 score on a scale
Standard Deviation 23.032
|
36.23 score on a scale
Standard Deviation 25.703
|
36.23 score on a scale
Standard Deviation 25.703
|
|
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
|
-0.50 score on a scale
Standard Deviation 6.536
|
0.50 score on a scale
Standard Deviation 0.883
|
2.28 score on a scale
Standard Deviation 4.110
|
|
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
|
-1.62 score on a scale
Standard Deviation 2.909
|
2.68 score on a scale
Standard Deviation 3.886
|
3.30 score on a scale
Standard Deviation 3.503
|
|
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
|
28.90 score on a scale
Standard Deviation 18.748
|
31.90 score on a scale
Standard Deviation 20.215
|
31.90 score on a scale
Standard Deviation 20.215
|
|
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
|
-1.94 score on a scale
Standard Deviation 3.889
|
2.47 score on a scale
Standard Deviation 3.661
|
2.55 score on a scale
Standard Deviation 3.486
|
|
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
|
1.56 score on a scale
Standard Deviation 3.591
|
2.30 score on a scale
Standard Deviation 3.866
|
0.02 score on a scale
Standard Deviation 2.334
|
|
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
|
-2.36 score on a scale
Standard Deviation 3.965
|
-0.30 score on a scale
Standard Deviation 1.137
|
-0.40 score on a scale
Standard Deviation 1.337
|
|
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
|
6.20 score on a scale
Standard Deviation 4.933
|
6.45 score on a scale
Standard Deviation 3.724
|
5.98 score on a scale
Standard Deviation 4.131
|
|
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 9.060
|
7.23 score on a scale
Standard Deviation 7.032
|
7.40 score on a scale
Standard Deviation 4.291
|
8.18 score on a scale
Standard Deviation 5.702
|
|
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
|
2.84 score on a scale
Standard Deviation 6.993
|
11.55 score on a scale
Standard Deviation 9.627
|
6.08 score on a scale
Standard Deviation 4.219
|
|
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
|
2.70 score on a scale
Standard Deviation 9.281
|
7.08 score on a scale
Standard Deviation 4.424
|
10.30 score on a scale
Standard Deviation 12.258
|
|
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
|
0.50 score on a scale
Standard Deviation 6.615
|
2.38 score on a scale
Standard Deviation 3.256
|
9.53 score on a scale
Standard Deviation 9.466
|
SECONDARY outcome
Timeframe: 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.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
|
2 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 Participants
Participants received, E2082 40 mg, tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=4 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
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.
|
|---|---|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for E2082
|
100 nanogram per milliliter (ng/mL)
Standard Deviation 25.1
|
617 nanogram per milliliter (ng/mL)
Standard Deviation 30.3
|
851 nanogram per milliliter (ng/mL)
Standard Deviation 91.8
|
—
|
SECONDARY outcome
Timeframe: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=4 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
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.
|
|---|---|---|---|---|
|
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2082
|
3.93 hour
Interval 1.0 to 7.82
|
3.96 hour
Interval 3.9 to 4.0
|
3.99 hour
Interval 1.88 to 7.88
|
—
|
SECONDARY outcome
Timeframe: Predose (within 2 hours prior to dosing) to 8 hours postdose on Day 1 of each treatment periodPopulation: 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.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=4 Participants
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 Participants
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
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.
|
|---|---|---|---|---|
|
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
|
3990 hour*nanogram per milliliter (h*ng/mL)
Standard Deviation 344
|
5750 hour*nanogram per milliliter (h*ng/mL)
Standard Deviation 787
|
—
|
Adverse Events
Treatment A: Placebo
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Treatment B: E2082 2.5 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Treatment C: E2082 25 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Open-label Treatment: E2082 40 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment A: Placebo
n=5 participants at risk
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 participants at risk
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 participants at risk
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 participants at risk
Participants received, E2082 40 mg tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
Eye disorders
Eye movement disorder
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Nervous system disorders
Disturbance in attention
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Nervous system disorders
Dysarthria
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
Other adverse events
| Measure |
Treatment A: Placebo
n=5 participants at risk
Participants received, E2082-matched placebo tablet, orally, once on Day 1 as per assigned Treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2082 2.5 mg
n=5 participants at risk
Participants received, E2082 2.5 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2082 25 mg
n=4 participants at risk
Participants received, E2082 25 mg tablet, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Open-label Treatment: E2082 40 mg
n=4 participants at risk
Participants received, E2082 40 mg tablet, orally, once on Day 1 of Treatment Period 4 in all the sequences.
|
|---|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Nervous system disorders
Dysarthria
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
25.0%
1/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Nervous system disorders
Headache
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Nervous system disorders
Somnolence
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
50.0%
2/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Psychiatric disorders
Aggression
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Psychiatric disorders
Anger
|
20.0%
1/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/5 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
25.0%
1/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
0.00%
0/4 • Up to 28 days after the last dose of study treatment on Day 1 in Treatment Period 4 (approximately Day 71)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place