Trial Outcomes & Findings for A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy (NCT NCT03603639)
NCT ID: NCT03603639
Last Updated: 2022-05-04
Results Overview
Photosensitivity described the presentation of an epileptiform electroencephalogram (EEG) response PPR from exposure to intermittent photic stimulation (IPS). SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The participants were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14 between the lowest to the highest frequencies of IPS that elicits epileptiform activity by EEG. The lower scores represented better outcomes. Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. Mean change from baseline in the SPR most sensitive eye condition was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3).
TERMINATED
PHASE2
6 participants
Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period
2022-05-04
Participant Flow
Participants took part in the study at 4 investigative sites in the United States from 27 July 2018 to 14 February 2019.
A total of 8 participants were screened, of which 2 were screen failures and 6 were randomized to receive study treatment. The study was terminated due to lack of photoparoxysmal response (PPR).
Participant milestones
| Measure |
Sequence 1: Placebo + E2730 40 mg + E2730 120 mg
Participants received, E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 40 milligram (mg) (Treatment B) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 2: E2730 40 mg + E2730 120 mg + Placebo
Participants received, E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 3: E2730 120 mg + Placebo + E2730 40 mg
Participants received, E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 -matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 4: Placebo + E2730 120 mg + E2730 40 mg
Participants received, E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 5: E2730 40 mg + Placebo + E2730 120 mg
Participants received, E2730 40 mg (Treatment B) capsule, once on Day 1 in Treatment Period 1, followed by E2730 -matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 6: E2730 120 mg + E2730 40 mg + Placebo
Participants received, E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (Day 1)
STARTED
|
1
|
1
|
1
|
1
|
1
|
1
|
|
Treatment Period 1 (Day 1)
COMPLETED
|
1
|
1
|
1
|
1
|
1
|
1
|
|
Treatment Period 1 (Day 1)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period (at Least 3 Weeks)
STARTED
|
1
|
1
|
1
|
1
|
1
|
1
|
|
Washout Period (at Least 3 Weeks)
COMPLETED
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Washout Period (at Least 3 Weeks)
NOT COMPLETED
|
0
|
0
|
1
|
1
|
1
|
1
|
|
Treatment Period 2 (Day 1)
STARTED
|
1
|
1
|
1
|
1
|
1
|
1
|
|
Treatment Period 2 (Day 1)
COMPLETED
|
1
|
1
|
1
|
1
|
1
|
1
|
|
Treatment Period 2 (Day 1)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (Day 1)
STARTED
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (Day 1)
COMPLETED
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (Day 1)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: Placebo + E2730 40 mg + E2730 120 mg
Participants received, E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 40 milligram (mg) (Treatment B) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 2: E2730 40 mg + E2730 120 mg + Placebo
Participants received, E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 3: E2730 120 mg + Placebo + E2730 40 mg
Participants received, E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 -matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 4: Placebo + E2730 120 mg + E2730 40 mg
Participants received, E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 5: E2730 40 mg + Placebo + E2730 120 mg
Participants received, E2730 40 mg (Treatment B) capsule, once on Day 1 in Treatment Period 1, followed by E2730 -matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
Sequence 6: E2730 120 mg + E2730 40 mg + Placebo
Participants received, E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1, followed by E2730 40 mg (Treatment B) capsule, orally, once on Day 1 in Treatment Period 2, followed by E2730-matched placebo (Treatment A) capsule, orally, once on Day 1 in Treatment Period 3. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
|---|---|---|---|---|---|---|
|
Washout Period (at Least 3 Weeks)
Adverse Event
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Washout Period (at Least 3 Weeks)
Study terminated by sponsor
|
0
|
0
|
1
|
0
|
1
|
1
|
Baseline Characteristics
A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy
Baseline characteristics by cohort
| Measure |
All Participants
n=6 Participants
Participants received E2730-matched placebo (Treatment A) or E2730 40 mg (Treatment B) or E2730 120 mg (Treatment C) capsule, orally, once on Day 1 in Treatment Period 1 to 3 as per assigned treatment sequence. A washout period of at least 3 weeks was maintained between all the treatment periods.
|
|---|---|
|
Age, Continuous
|
28.0 years
STANDARD_DEVIATION 7.32 • n=5 Participants
|
|
Age, Customized
greater than or equal to (>=) 18 to less than (<) 40
|
5 Participants
n=5 Participants
|
|
Age, Customized
>= 40 to < 60
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 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
|
6 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
|
6 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) pre-dose and at 8 hours post-dose on Day 1 of each treatment periodPopulation: The pharmacodynamic (PD) analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Photosensitivity described the presentation of an epileptiform electroencephalogram (EEG) response PPR from exposure to intermittent photic stimulation (IPS). SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The participants were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14 between the lowest to the highest frequencies of IPS that elicits epileptiform activity by EEG. The lower scores represented better outcomes. Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. Mean change from baseline in the SPR most sensitive eye condition was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3).
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Mean Change From Baseline in the Standard Photosensitivity Response (SPR) in the Most Sensitive Eye Condition at 8 Hours Post-dose on Day 1 of Each Treatment Period
Baseline
|
7.80 units on a scale
Standard Deviation 5.495
|
5.50 units on a scale
Standard Deviation 6.137
|
9.00 units on a scale
Standard Deviation 3.391
|
|
Mean Change From Baseline in the Standard Photosensitivity Response (SPR) in the Most Sensitive Eye Condition at 8 Hours Post-dose on Day 1 of Each Treatment Period
Change at 8 hour post-dose
|
-0.12 units on a scale
Standard Deviation 1.677
|
0.65 units on a scale
Standard Deviation 0.755
|
1.00 units on a scale
Standard Deviation 2.839
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment periodPopulation: The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Photosensitivity described the presentation of an epileptiform EEG response PPR from exposure to IPS. SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open). The participants were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14. Lower scores represented better outcomes. Mean change from baseline in the SPR in each of the 3 eye conditions (Eye Closure, Eyes Closed, and Eyes Opened) was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3).
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Open: Change at 8 hours post-dose
|
0.76 units on a scale
Standard Deviation 1.846
|
0.05 units on a scale
Standard Deviation 1.716
|
1.20 units on a scale
Standard Deviation 2.874
|
|
Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period
Eye Closure: At Baseline
|
8.00 units on a scale
Standard Deviation 6.000
|
5.75 units on a scale
Standard Deviation 6.551
|
9.20 units on a scale
Standard Deviation 3.114
|
|
Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period
Eye Closure: Change at 8 hours post-dose
|
0.12 units on a scale
Standard Deviation 1.579
|
0.65 units on a scale
Standard Deviation 1.279
|
0.60 units on a scale
Standard Deviation 2.054
|
|
Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Closed: At Baseline
|
7.60 units on a scale
Standard Deviation 5.225
|
5.25 units on a scale
Standard Deviation 6.021
|
8.80 units on a scale
Standard Deviation 3.114
|
|
Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Closed: Change at 8 hours post-dose
|
-0.24 units on a scale
Standard Deviation 1.711
|
0.90 units on a scale
Standard Deviation 1.149
|
0.92 units on a scale
Standard Deviation 2.969
|
|
Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Open: At Baseline
|
4.20 units on a scale
Standard Deviation 5.762
|
4.75 units on a scale
Standard Deviation 6.185
|
7.00 units on a scale
Standard Deviation 2.646
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment periodPopulation: The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Time to onset of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean change from baseline SPR data across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants (not for each participant) was at least 3 units below the mean SPR at baseline. Photosensitivity response were essentially intermittent photic stimulation IPS assessments, is a form of visual stimulation, when the participants are flashed with light on their eyes intermittently at different hertz.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Time to Onset of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Closed
|
NA hours
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.
|
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.
|
|
Time to Onset of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Opened
|
NA hours
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.
|
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.
|
|
Time to Onset of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eye Closure
|
NA hours
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.
|
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.
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment periodPopulation: The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Duration of mean photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) was determined from mean change from baseline SPR data across participants. Duration of suppression was defined as the difference in hours between the onset of suppression and the end of suppression of photosensitivity across participants. The onset of mean suppression was defined as the first time point at which the mean SPR across participants (not for each participant) was at least 3 units below the mean SPR at baseline. The end of mean suppression was defined as the last time (second time) with two successive reductions in mean SPR of at least 3 units lower than the mean SPR at baseline. SPR was a standardized derived measure of range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14. Lower scores represented better outcomes.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Closed: Duration
|
NA hours
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.
|
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.
|
|
Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Open: Duration
|
NA hours
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.
|
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.
|
|
Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eye Closure: Duration
|
NA hours
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.
|
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.
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment periodPopulation: The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Complete suppression was defined as a SPR reduction to 0 over at least 1 time point for all three eye conditions. Partial response was defined as a reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response was defined as the response not meeting complete suppression or partial suppression definitions.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Number of Participants With Complete Suppression, Partial Response, and no Response of SPR up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Complete Suppression
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Complete Suppression, Partial Response, and no Response of SPR up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Partial Response
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Complete Suppression, Partial Response, and no Response of SPR up to 8 Hours Post-dose on Day 1 of Each Treatment Period
No Response
|
4 Participants
|
4 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment periodPopulation: The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Maximum change from baseline of photosensitivity response in each of the 3 eye conditions (eye closure, eyes closed, and eyes open condition) across participants (not for each participant) were reported. Photosensitivity described the presentation of an epileptiform EEG response (PPR) from exposure to IPS. SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. IPS-EEG assessments determine the range of frequencies of IPS that elicited an epileptiform EEG response. Each IPS-EEG assessment was conducted in all 3 eye conditions (eye closure, eyes closed, and eyes open). The participants were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14. Lower scores representing better outcomes.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eye Closure: Baseline
|
14.0 units on a scale
|
14.0 units on a scale
|
13.0 units on a scale
|
|
Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eye Closure: Maximum change from baseline
|
2.6 units on a scale
|
2.0 units on a scale
|
4.0 units on a scale
|
|
Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Closed: Baseline
|
13.0 units on a scale
|
13.0 units on a scale
|
12.0 units on a scale
|
|
Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Closed: Maximum change from baseline
|
1.6 units on a scale
|
2.4 units on a scale
|
6.0 units on a scale
|
|
Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Open: Baseline
|
11.0 units on a scale
|
13.0 units on a scale
|
10.0 units on a scale
|
|
Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period
Eyes Open: Maximum change from baseline
|
3.8 units on a scale
|
2.2 units on a scale
|
5.0 units on a scale
|
SECONDARY outcome
Timeframe: First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71)Population: The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE is continuous. An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
3 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71)Population: The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
Vital signs parameters included systolic and diastolic Blood Pressure, pulse rate, respiratory rate, and temperature were assessed. Clinically significant values were defined as values above or below the normal reference range post-dose. Number of participants with clinically significant change from baseline values for vital signs was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71)Population: The safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
Laboratory assessment included clinical chemistry, hematology and liver function test parameters. Clinically significant values were defined as values above or below the normal reference range post-dose. Number of participants with clinically significant change from baseline values for laboratory parameters: clinical chemistry, hematology and liver function test are reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test
Clinical Chemistry
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test
Hematology
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test
Liver Function Test
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Days 1, 22 and 43: 0-8 hours post-dosePopulation: The pharmacokinetic (PK) analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PK data to derive at least 1 PK parameter.
Outcome measures
| Measure |
Treatment A: Placebo
n=4 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=5 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite
E2730
|
737 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 18.4
|
2440 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 18.5
|
—
|
|
Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite
N-acetyl metabolite
|
0.672 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 62.3
|
1.89 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 38.2
|
—
|
SECONDARY outcome
Timeframe: Days 1, 22 and 43: 0-8 hours post-dosePopulation: The PK analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PK data to derive at least 1 PK parameter.
Outcome measures
| Measure |
Treatment A: Placebo
n=4 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=5 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite
E2730
|
4.15 hours
Interval 2.02 to 5.92
|
1.78 hours
Interval 0.1 to 7.93
|
—
|
|
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite
N-acetyl metabolite
|
1.65 hours
Interval 1.03 to 4.2
|
4.00 hours
Interval 0.1 to 7.93
|
—
|
SECONDARY outcome
Timeframe: Days 1, 22 and 43: 0-8 hours post-dosePopulation: The PK analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PK data to derive at least 1 PK parameter.
Outcome measures
| Measure |
Treatment A: Placebo
n=4 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=5 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite
E2730
|
5140 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 18.4
|
15100 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 23.2
|
—
|
|
AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite
N-acetyl metabolite
|
2.48 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 183
|
10.0 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 37.3
|
—
|
SECONDARY outcome
Timeframe: Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment periodPopulation: The PD analysis set included randomized participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter.
Relationship between PK parameters of E2730 and PD parameters (onset, maximum change, and duration of impact on photosensitivity) were to be assessed using model-based approach. The PK-PD analysis dataset were to be used and included in examination of the relationship of PK of E2730 and change in PPR response (example, time of onset, maximum change, and duration of PPR; Bond and Lader data).
Outcome measures
| Measure |
Treatment A: Placebo
n=5 Participants
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 Participants
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 Participants
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity
|
NA correlation coefficient
Relationship Between PK Parameters of E2730 and PD parameters (onset, maximum change, and duration of impact on photosensitivity) cannot be determined because no PPR and dose response was observed during assessment period. Hence, the PK-PD analysis was not conducted.
|
NA correlation coefficient
Relationship Between PK Parameters of E2730 and PD parameters (onset, maximum change, and duration of impact on photosensitivity) cannot be determined because no PPR and dose response was observed during assessment period. Hence, the PK-PD analysis was not conducted.
|
NA correlation coefficient
Relationship Between PK Parameters of E2730 and PD parameters (onset, maximum change, and duration of impact on photosensitivity) cannot be determined because no PPR and dose response was observed during assessment period. Hence, the PK-PD analysis was not conducted.
|
Adverse Events
Treatment A: Placebo
Treatment B: E2730 40 mg
Treatment C: E2730 120 mg
Serious adverse events
| Measure |
Treatment A: Placebo
n=5 participants at risk
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 participants at risk
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 participants at risk
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Eye disorders
Eyelid myoclonus
|
0.00%
0/5 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/4 • Up to 28 days after last dose of study drug (Day 71)
|
20.0%
1/5 • Up to 28 days after last dose of study drug (Day 71)
|
Other adverse events
| Measure |
Treatment A: Placebo
n=5 participants at risk
Participants received, E2730-matched placebo capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment B: E2730 40 mg
n=4 participants at risk
Participants received, E2730 40 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
Treatment C: E2730 120 mg
n=5 participants at risk
Participants received, E2730 120 mg capsule, orally, once on Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
20.0%
1/5 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/4 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/5 • Up to 28 days after last dose of study drug (Day 71)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/5 • Up to 28 days after last dose of study drug (Day 71)
|
25.0%
1/4 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/5 • Up to 28 days after last dose of study drug (Day 71)
|
|
Investigations
White blood cells urine positive
|
20.0%
1/5 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/4 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/5 • Up to 28 days after last dose of study drug (Day 71)
|
|
Nervous system disorders
Dizziness postural
|
20.0%
1/5 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/4 • Up to 28 days after last dose of study drug (Day 71)
|
0.00%
0/5 • Up to 28 days after last dose of study drug (Day 71)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place