Trial Outcomes & Findings for A Study to Explore the Safety And Tolerability of Doses of E2007 Up to a Maximum of 8 mg In Patients With Parkinson's Disease Who Experience End-of-Dose Wearing Off Motor Fluctuations (NCT NCT00165789)
NCT ID: NCT00165789
Last Updated: 2015-06-02
Results Overview
Treatment-emergent Adverse Events (TEAEs) were defined as those adverse events (AEs) that started on or after the first dose of study medication until the end of the study. Information on any AEs were recorded throughout the study after informed consent had been signed and included abnormal clinical laboratory tests, vital sign measurements and physical examinations. Note: Safety/tolerability info captured in Adverse Event section.
COMPLETED
PHASE2
75 participants
Through end of study
2015-06-02
Participant Flow
Participant milestones
| Measure |
Cohort 1 - Placebo
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2- Placebo
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
20
|
12
|
35
|
|
Overall Study
COMPLETED
|
8
|
16
|
11
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
4
|
1
|
14
|
Reasons for withdrawal
| Measure |
Cohort 1 - Placebo
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2- Placebo
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
3
|
0
|
12
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
2
|
Baseline Characteristics
A Study to Explore the Safety And Tolerability of Doses of E2007 Up to a Maximum of 8 mg In Patients With Parkinson's Disease Who Experience End-of-Dose Wearing Off Motor Fluctuations
Baseline characteristics by cohort
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=12 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=35 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
67.6 Years
STANDARD_DEVIATION 10.43 • n=5 Participants
|
68.5 Years
STANDARD_DEVIATION 7.78 • n=7 Participants
|
68.5 Years
STANDARD_DEVIATION 12.71 • n=5 Participants
|
67.5 Years
STANDARD_DEVIATION 10.48 • n=4 Participants
|
68.025 Years
STANDARD_DEVIATION 10.35 • n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Through end of studyPopulation: Safety Population was the primary population for analysis defined as all subjects who completed the Baseline Phase and who received at least 1 dose of double-blind study medication.
Treatment-emergent Adverse Events (TEAEs) were defined as those adverse events (AEs) that started on or after the first dose of study medication until the end of the study. Information on any AEs were recorded throughout the study after informed consent had been signed and included abnormal clinical laboratory tests, vital sign measurements and physical examinations. Note: Safety/tolerability info captured in Adverse Event section.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=12 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=35 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Any TEAE
|
7 Participants
|
18 Participants
|
8 Participants
|
32 Participants
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
The Unified Parkinson's Disease Rating Scale (UPDRS) consisted of 4 subsections used to assess symptoms and signs of Parkinson's disease, with an overall scale range of 0-147. Individual subsections included: I. Mentation, behavior, and mood (0-16); II. Activities of daily living assessed in both the "on" and "off" state (0-52); III. Motor examination (0-56); and IV. Complications of therapy assessed in the "on" fluctuations and dyskinesias (0-23). Each subsection included subscales that ranged from 0 (best possible outcome) to 1 or 4 (worst possible outcome), with the total score of subsection equaling the sum of the scores of the subscales and the overall UPDRS score equaling the sum of the scores of the 4 subsections (higher score indicating more severe Parkinson's Disease).
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=21 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in "on" State of UPDRS Scores
Activities of Daily Living
|
0.75 Scores on a Scale
Standard Deviation 5.751
|
-0.27 Scores on a Scale
Standard Deviation 3.615
|
1 Scores on a Scale
Standard Deviation 4.648
|
0.24 Scores on a Scale
Standard Deviation 2.755
|
|
Change From Baseline to Day 70 in "on" State of UPDRS Scores
Motor Examinations
|
-6.38 Scores on a Scale
Standard Deviation 9.149
|
-3.93 Scores on a Scale
Standard Deviation 5.365
|
-0.73 Scores on a Scale
Standard Deviation 5.587
|
-1.14 Scores on a Scale
Standard Deviation 5.452
|
|
Change From Baseline to Day 70 in "on" State of UPDRS Scores
Complications of Therapy
|
-0.63 Scores on a Scale
Standard Deviation 4.241
|
-1.13 Scores on a Scale
Standard Deviation 1.685
|
-0.73 Scores on a Scale
Standard Deviation 3.467
|
0.1 Scores on a Scale
Standard Deviation 2.663
|
|
Change From Baseline to Day 70 in "on" State of UPDRS Scores
Overall Score
|
-7.13 Scores on a Scale
Standard Deviation 13.601
|
-5.33 Scores on a Scale
Standard Deviation 6.355
|
-1.18 Scores on a Scale
Standard Deviation 10.806
|
0.05 Scores on a Scale
Standard Deviation 7.117
|
|
Change From Baseline to Day 70 in "on" State of UPDRS Scores
Mentation, Behavior, and Mood
|
-0.88 Scores on a Scale
Standard Deviation 0.641
|
0 Scores on a Scale
Standard Deviation 1.134
|
-0.73 Scores on a Scale
Standard Deviation 1.104
|
0.86 Scores on a Scale
Standard Deviation 1.526
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Absolute "Off" Time
|
-0.94 Hour
Standard Deviation 2.162
|
-2.11 Hour
Standard Deviation 3.714
|
-1.27 Hour
Standard Deviation 2.411
|
-0.93 Hour
Standard Deviation 2.28
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Absolute "on" Time With Non-troublesome Dyskinesias
|
0 Hours
Standard Deviation 2.372
|
-0.51 Hours
Standard Deviation 1.634
|
-0.14 Hours
Standard Deviation 1.38
|
0.4 Hours
Standard Deviation 1.536
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Absolute "on" Time With Troublesome Dyskinesias
|
-0.96 Hours
Standard Deviation 1.471
|
0.57 Hours
Standard Deviation 1.635
|
-0.14 Hours
Standard Deviation 1.074
|
-0.48 Hours
Standard Deviation 2.104
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
The Goetz/Rush scale was used to rate severity during performance of tasks intended to elicit dyskinesias, and provided an objective rating of dyskinesias during activities of daily living.The tasks included a sitting exercise, mental calculations, drinking, dressing, and walking. A 5-point scale was used: 0=absent; 1=minimal severity, no interference with voluntary motor acts; 2=dyskinesias, may impair voluntary movements but the subject was capable of efficiently completing the motor task; 3=intense dyskinesias, interference with movement control and completion of the motor task was greatly limited; 4= violent dyskinesias, incompatible with the completion of the motor task. A lower score indicated less difficulty performing the tasks.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=16 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=21 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Goetz/Rush Score
|
-1.63 Scores on a Scale
Standard Deviation 2.875
|
0.63 Scores on a Scale
Standard Deviation 1.784
|
-0.3 Scores on a Scale
Standard Deviation 1.79
|
-0.4 Scores on a Scale
Standard Deviation 1.77
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Percent "Off" Time
|
-7.46 Percentage of the Day
Standard Deviation 14.614
|
-13.91 Percentage of the Day
Standard Deviation 23.06
|
-7.9 Percentage of the Day
Standard Deviation 15.114
|
-6 Percentage of the Day
Standard Deviation 12.388
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Percent "on" Time
|
-6.77 Percentage of the Day
Standard Deviation 10.408
|
3.07 Percentage of the Day
Standard Deviation 9.006
|
-0.74 Percentage of the Day
Standard Deviation 5.792
|
-3.16 Percentage of the Day
Standard Deviation 12.953
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population. Change from Baseline only reflect participants who completed the assessment at Baseline and Day 70.
Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=15 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=11 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Change From Baseline to Day 70 in Percent "on" Time With Non-troublesome Dyskinesias
|
0.28 Percentage of the Day
Standard Deviation 15.672
|
-2.49 Percentage of the Day
Standard Deviation 9.603
|
-0.63 Percentage of the Day
Standard Deviation 7.653
|
2.75 Percentage of the Day
Standard Deviation 9.935
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population
The disability of dyskinesia was determined from question 33 (part 4) of the UPDRS assessment. It asks how disabling are the dyskinesias, and uses a 5-part scale: 0=Not disabling, 1=MIldly disabling, 2=Moderately disabling, 3=Severely disabling, 4=Completely disabling. Lower scores represented more normal functioning.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=12 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=35 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, Completely Disabling (n=8,20,12,35)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, Not Disabling (n=8,16,11,21)
|
6 Participants
|
10 Participants
|
6 Participants
|
14 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, Not Disabling (n=8,20,12,35)
|
5 Participants
|
13 Participants
|
8 Participants
|
18 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, Mildly Disabling (n=8,20,12,35)
|
1 Participants
|
3 Participants
|
1 Participants
|
13 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, Moderately Disabling (n=8,20,12,35)
|
1 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, Severely Disabling (n=8,20,12,35)
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, Mildly Disabling (n=8,16,11,21)
|
1 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, Moderately Disabling (n=8,16,11,21)
|
0 Participants
|
2 Participants
|
1 Participants
|
4 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, Severely Disabling (n=8,16,11,21)
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Disability of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, Completely Disabling (n=8,16,11,21)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and Day 70Population: Safety Population
The duration of dyskinesia was determined from question 32 (part 4) of the UPDRS assessment. It asks what proportion of the waking day are dyskinesias present, and uses a 5-part scale: 0 = None, 1 = 1-25% of day, 2 = 26-50% of day, 3 = 51-75% of day, 4 = 76-100% of day. Lower scores represented more normal functioning.
Outcome measures
| Measure |
Cohort 1 - Placebo
n=8 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=20 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=12 Participants
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=35 Participants
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, 1 to 25% of Day (n=8,20,12,35)
|
3 Participants
|
7 Participants
|
3 Participants
|
15 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, 26 to 50% of Day (n=8,20,12,35)
|
3 Participants
|
3 Participants
|
4 Participants
|
6 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, 51 to 75% of Day (n=8,20,12,35)
|
0 Participants
|
5 Participants
|
1 Participants
|
1 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, None (n=8,16,11,21)
|
1 Participants
|
6 Participants
|
4 Participants
|
7 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, 1 to 25% of Day (n=8,16,11,21)
|
5 Participants
|
5 Participants
|
5 Participants
|
9 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, 51 to 75% of Day (n=8,16,11,21)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, None (n=8,20,12,35)
|
1 Participants
|
5 Participants
|
4 Participants
|
11 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Baseline, 76 to 100% of Day (n=8,20,12,35)
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, 26 to 50% of Day (n=8,16,11,21)
|
2 Participants
|
4 Participants
|
2 Participants
|
5 Participants
|
|
Duration of Dyskinesia From UPDRS at Baseline and Day 70
Day 70, 76 to 100% of Day (n=8,16,11,21)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort 1 - Placebo
Cohort 1 - Perampanel
Cohort 2 - Placebo
Cohort 2 - Perampanel
Serious adverse events
| Measure |
Cohort 1 - Placebo
n=8 participants at risk
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=20 participants at risk
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=12 participants at risk
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=35 participants at risk
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
PELVIC FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
TIBIA FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
ELECTROCARDIOGRAM ABNORMAL
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Nervous system disorders
HEMIPARESIS
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Nervous system disorders
PARKINSON'S DISEASE
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Psychiatric disorders
INSOMNIA
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
Other adverse events
| Measure |
Cohort 1 - Placebo
n=8 participants at risk
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 1 - Perampanel
n=20 participants at risk
Perampanel started at 2 mg once daily for 2 weeks, followed by 3 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 4 weeks.
|
Cohort 2 - Placebo
n=12 participants at risk
Placebo matching Perampanel dosing once daily for 10 weeks.
|
Cohort 2 - Perampanel
n=35 participants at risk
Perampanel started at 2 mg once daily for 2 weeks, followed by 4 mg once daily for 2 weeks, followed by 6 mg once daily for 2 weeks, followed by 8 mg once daily for 4 weeks.
|
|---|---|---|---|---|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
12.5%
1/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Cardiac disorders
ATRIAL FLUTTER
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Cardiac disorders
ATRIOVENTRICULAR BLOCK FIRST DEGREE
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
2.9%
1/35
|
|
Cardiac disorders
PALPITATIONS
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Cardiac disorders
SUPRAVENTRICULAR EXTRASYSTOLES
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Cardiac disorders
TACHYCARDIA
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Ear and labyrinth disorders
EAR DISCOMFORT
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Ear and labyrinth disorders
EAR PAIN
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Ear and labyrinth disorders
VERTIGO
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Eye disorders
LACRIMATION INCREASED
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
GASTRITIS ATROPHIC
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
HIATUS HERNIA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/8
|
20.0%
4/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/8
|
10.0%
2/20
|
0.00%
0/12
|
5.7%
2/35
|
|
General disorders
ASTHENIA
|
0.00%
0/8
|
5.0%
1/20
|
8.3%
1/12
|
5.7%
2/35
|
|
General disorders
DIFFICULTY IN WALKING
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
General disorders
FATIGUE
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
2.9%
1/35
|
|
General disorders
GAIT DISTURBANCE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
General disorders
OEDEMA PERIPHERAL
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Infections and infestations
DENTAL CARIES
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Infections and infestations
HELICOBACTER INFECTION
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Infections and infestations
LARYNGITIS
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Infections and infestations
NASOPHARYNGITIS
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Infections and infestations
SINUSITIS
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Infections and infestations
URINARY TRACT INFECTION
|
12.5%
1/8
|
10.0%
2/20
|
16.7%
2/12
|
5.7%
2/35
|
|
Injury, poisoning and procedural complications
CONTUSION
|
0.00%
0/8
|
10.0%
2/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/8
|
10.0%
2/20
|
0.00%
0/12
|
8.6%
3/35
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
PELVIC FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
PROCEDURAL PAIN
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
TIBIA FRACTURE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
BLOOD CHOLESTEROL INCREASED
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
0.00%
0/8
|
10.0%
2/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Investigations
BLOOD CREATININE INCREASED
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
BLOOD PRESSURE DECREASED
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
5.7%
2/35
|
|
Investigations
BLOOD PRESSURE INCREASED
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
2.9%
1/35
|
|
Investigations
ELECTROCARDIOGRAM CHANGE
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Investigations
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
HEART RATE INCREASED
|
0.00%
0/8
|
5.0%
1/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Investigations
URINARY CASTS
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
URINE LEUKOCYTE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Investigations
WHITE BLOOD CELLS URINE POSITIVE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Musculoskeletal and connective tissue disorders
MUSCLE RIGIDITY
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL STIFFNESS
|
0.00%
0/8
|
10.0%
2/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Musculoskeletal and connective tissue disorders
POSTURE ABNORMAL
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
SHOULDER PAIN
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
TENDONITIS
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
BALANCE DISORDER
|
12.5%
1/8
|
10.0%
2/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Nervous system disorders
BRADYKINESIA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
CHOREA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
DISTURBANCE IN ATTENTION
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
DIZZINESS
|
12.5%
1/8
|
20.0%
4/20
|
8.3%
1/12
|
28.6%
10/35
|
|
Nervous system disorders
DIZZINESS POSTURAL
|
0.00%
0/8
|
0.00%
0/20
|
16.7%
2/12
|
0.00%
0/35
|
|
Nervous system disorders
DROOLING
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
DYSGEUSIA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
DYSKINESIA
|
12.5%
1/8
|
10.0%
2/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Nervous system disorders
DYSTONIA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Nervous system disorders
HEADACHE
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
8.6%
3/35
|
|
Nervous system disorders
HYPERREFLEXIA
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
MUSCLE SPASTICITY
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Nervous system disorders
NYSTAGMUS
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
2.9%
1/35
|
|
Nervous system disorders
PARKINSON'S DISEASE
|
12.5%
1/8
|
5.0%
1/20
|
8.3%
1/12
|
14.3%
5/35
|
|
Nervous system disorders
SEDATION
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
11.4%
4/35
|
|
Nervous system disorders
SOMNOLENCE
|
25.0%
2/8
|
25.0%
5/20
|
25.0%
3/12
|
31.4%
11/35
|
|
Nervous system disorders
TREMOR
|
12.5%
1/8
|
5.0%
1/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Nervous system disorders
TUNNEL VISION
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Psychiatric disorders
ABNORMAL DREAMS
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Psychiatric disorders
DELUSION
|
0.00%
0/8
|
10.0%
2/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/8
|
5.0%
1/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Psychiatric disorders
HALLUCINATION,VISUAL
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Psychiatric disorders
IMPULSIVE BEHAVIOUR
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Psychiatric disorders
INITIAL INSOMNIA
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Psychiatric disorders
INSOMNIA
|
0.00%
0/8
|
10.0%
2/20
|
8.3%
1/12
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/8
|
5.0%
1/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
DERMATITIS CONTACT
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
2.9%
1/35
|
|
Skin and subcutaneous tissue disorders
ECCHYMOSIS
|
0.00%
0/8
|
0.00%
0/20
|
8.3%
1/12
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
2.9%
1/35
|
|
Skin and subcutaneous tissue disorders
SKIN LESION
|
0.00%
0/8
|
5.0%
1/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
SWELLING FACE
|
12.5%
1/8
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/35
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/8
|
0.00%
0/20
|
0.00%
0/12
|
5.7%
2/35
|
|
Vascular disorders
HYPOTENSION
|
0.00%
0/8
|
5.0%
1/20
|
8.3%
1/12
|
8.6%
3/35
|
|
Vascular disorders
ORTHOSTATIC HYPOTENSION
|
12.5%
1/8
|
5.0%
1/20
|
0.00%
0/12
|
5.7%
2/35
|
Additional Information
Eisai Inc.
Eisai Call Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place