Trial Outcomes & Findings for Dose-Tolerability Titration Study to Evaluate The Efficacy And Safety Of Perampanel (E2007) In Patients With Post-Herpetic Neuralgia (PHN) (NCT NCT00592774)

Last Updated: 2013-02-15

Results Overview

Average pain scores are based on pain intensity (11-point Likert-type numerical scale, where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain score for baseline was calculated using the average of the last 7 scores prior to randomization, and the average pain score for Week 15 was computed using the average of the last 7 on-treatment scores prior to Week 15, and they were reported by treatment group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

146 participants

Primary outcome timeframe

Baseline and Week 15

Results posted on

2013-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Cohort 1 Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Overall Study STARTED	26	53	22	22	23
Overall Study COMPLETED	15	21	18	8	9
Overall Study NOT COMPLETED	11	32	4	14	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Cohort 1 Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Overall Study Adverse Event	5	19	2	14	8
Overall Study Protocol Violation	0	1	0	0	1
Overall Study Withdrawal by Subject	3	7	0	0	0
Overall Study Lack of Efficacy	3	3	0	0	2
Overall Study Physician Decision	0	1	1	0	1
Overall Study Other	0	1	1	0	2

Baseline Characteristics

Dose-Tolerability Titration Study to Evaluate The Efficacy And Safety Of Perampanel (E2007) In Patients With Post-Herpetic Neuralgia (PHN)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Total n=146 Participants Total of all reporting groups
Age, Customized <65 years	10 Participants n=5 Participants	15 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants	42 Participants n=8 Participants
Age, Customized ≥65 to <75 years	8 Participants n=5 Participants	15 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	3 Participants n=21 Participants	35 Participants n=8 Participants
Age, Customized ≥75 years	8 Participants n=5 Participants	23 Participants n=7 Participants	11 Participants n=5 Participants	16 Participants n=4 Participants	11 Participants n=21 Participants	69 Participants n=8 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	31 Participants n=7 Participants	8 Participants n=5 Participants	11 Participants n=4 Participants	14 Participants n=21 Participants	75 Participants n=8 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	22 Participants n=7 Participants	14 Participants n=5 Participants	11 Participants n=4 Participants	9 Participants n=21 Participants	71 Participants n=8 Participants
Race/Ethnicity, Customized White	25 Participants n=5 Participants	43 Participants n=7 Participants	20 Participants n=5 Participants	21 Participants n=4 Participants	18 Participants n=21 Participants	127 Participants n=8 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	9 Participants n=8 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	7 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline and Week 15

Population: Intent-to-Treat (ITT) Population- group of subjects who were randomized, took study drug, and had at least 1 efficacy assessment at Baseline. The modified Baseline Observation Carried Forward (BOCF) method was used.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Change From Baseline in Average Pain Scores to Week 15/ End of Treatment (EOT) (Including Modified BOCF Data)	-0.55 Scores on a scale Standard Deviation 1.56	-1.30 Scores on a scale Standard Deviation 2.13	-0.95 Scores on a scale Standard Deviation 1.77	-0.50 Scores on a scale Standard Deviation 1.35	-1.01 Scores on a scale Standard Deviation 1.52

PRIMARY outcome

Timeframe: Baseline and Week 15

Population: ITT Population (Modified BOCF)

A responder was a participant with at least 30 percent reduction in average pain scores, using modified BOCF, based on pain intensity (11-point Likert-type numerical scale where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain score for baseline was calculated using the average of the last 7 scores prior to randomization, and the average pain score for Week 15 was computed using the average of the last 7 on-treatment scores prior to Week 15, and they were reported by treatment group.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Responder Rate: Subjects With at Least 30 Percent Reduction in Pain Responders (Yes)	19.2 Percentage of Participants	28.3 Percentage of Participants	22.7 Percentage of Participants	13.6 Percentage of Participants	26.1 Percentage of Participants
Responder Rate: Subjects With at Least 30 Percent Reduction in Pain Non-Responders (No)	80.8 Percentage of Participants	71.7 Percentage of Participants	77.3 Percentage of Participants	86.4 Percentage of Participants	73.9 Percentage of Participants

PRIMARY outcome

Timeframe: Baseline and Week 15

Population: ITT Population (Modified BOCF)

A responder was a participant with at least 50 percent reduction in average pain scores, using modified BOCF, based on pain intensity (11-point Likert-type numerical scale where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain score for baseline was calculated using the average of the last 7 scores prior to randomization, and the average pain score for Week 15 was computed using the average of the last 7 on-treatment scores prior to Week 15, and they were reported by treatment group.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Responder Rate: Subjects With at Least 50 Percent Reduction in Pain Responders (Yes)	11.5 Percentage of Participants	20.8 Percentage of Participants	13.6 Percentage of Participants	9.1 Percentage of Participants	13.0 Percentage of Participants
Responder Rate: Subjects With at Least 50 Percent Reduction in Pain Non-Responders (No)	88.5 Percentage of Participants	79.2 Percentage of Participants	86.4 Percentage of Participants	90.9 Percentage of Participants	87.0 Percentage of Participants

PRIMARY outcome

Timeframe: Week 1 through Week 16

Population: ITT Population

Change from baseline in average pain scores by week based on pain intensity (11-point Likert-type numerical scale where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain scores were calculated as the average of available scores in each week, and were reported by treatment group.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Change From Baseline in Average Pain Scores by Week Week 1	-0.25 Scores on a scale Standard Deviation 0.66	-0.35 Scores on a scale Standard Deviation 1.03	-0.43 Scores on a scale Standard Deviation 0.88	-0.44 Scores on a scale Standard Deviation 0.75	-0.55 Scores on a scale Standard Deviation 0.71
Change From Baseline in Average Pain Scores by Week Week 2	-0.39 Scores on a scale Standard Deviation 1.11	-0.60 Scores on a scale Standard Deviation 1.29	-0.64 Scores on a scale Standard Deviation 1.19	-0.86 Scores on a scale Standard Deviation 1.19	-0.74 Scores on a scale Standard Deviation 1.23
Change From Baseline in Average Pain Scores by Week Week 3	-0.68 Scores on a scale Standard Deviation 1.20	-1.01 Scores on a scale Standard Deviation 1.61	-0.74 Scores on a scale Standard Deviation 1.31	-1.22 Scores on a scale Standard Deviation 1.53	-1.19 Scores on a scale Standard Deviation 1.32
Change From Baseline in Average Pain Scores by Week Week 4	-0.82 Scores on a scale Standard Deviation 1.70	-1.29 Scores on a scale Standard Deviation 1.88	-0.89 Scores on a scale Standard Deviation 1.48	-1.64 Scores on a scale Standard Deviation 1.68	-1.68 Scores on a scale Standard Deviation 1.49
Change From Baseline in Average Pain Scores by Week Week 5	-1.13 Scores on a scale Standard Deviation 1.93	-1.46 Scores on a scale Standard Deviation 1.93	-0.74 Scores on a scale Standard Deviation 1.58	-1.68 Scores on a scale Standard Deviation 1.93	-1.23 Scores on a scale Standard Deviation 1.43
Change From Baseline in Average Pain Scores by Week Week 6	-0.81 Scores on a scale Standard Deviation 1.37	-1.39 Scores on a scale Standard Deviation 1.96	-0.92 Scores on a scale Standard Deviation 1.66	-1.53 Scores on a scale Standard Deviation 2.23	-1.31 Scores on a scale Standard Deviation 1.43
Change From Baseline in Average Pain Scores by Week Week 7	-0.80 Scores on a scale Standard Deviation 1.57	-1.74 Scores on a scale Standard Deviation 2.12	-1.21 Scores on a scale Standard Deviation 1.74	-1.52 Scores on a scale Standard Deviation 2.32	-1.50 Scores on a scale Standard Deviation 1.67
Change From Baseline in Average Pain Scores by Week Week 8	-0.68 Scores on a scale Standard Deviation 1.43	-1.92 Scores on a scale Standard Deviation 2.32	-1.03 Scores on a scale Standard Deviation 1.66	-1.46 Scores on a scale Standard Deviation 2.21	-1.68 Scores on a scale Standard Deviation 2.01
Change From Baseline in Average Pain Scores by Week Week 9	-0.53 Scores on a scale Standard Deviation 1.43	-1.99 Scores on a scale Standard Deviation 2.34	-1.08 Scores on a scale Standard Deviation 1.79	-1.24 Scores on a scale Standard Deviation 1.88	-1.73 Scores on a scale Standard Deviation 2.24
Change From Baseline in Average Pain Scores by Week Week 10	-0.88 Scores on a scale Standard Deviation 1.60	-2.17 Scores on a scale Standard Deviation 2.30	-1.14 Scores on a scale Standard Deviation 1.92	-1.48 Scores on a scale Standard Deviation 1.71	-1.36 Scores on a scale Standard Deviation 2.38
Change From Baseline in Average Pain Scores by Week Week 11	-0.96 Scores on a scale Standard Deviation 1.67	-2.33 Scores on a scale Standard Deviation 2.28	-1.01 Scores on a scale Standard Deviation 1.64	-1.98 Scores on a scale Standard Deviation 1.63	-1.46 Scores on a scale Standard Deviation 2.51
Change From Baseline in Average Pain Scores by Week Week 12	-0.99 Scores on a scale Standard Deviation 1.78	-2.52 Scores on a scale Standard Deviation 2.36	-1.01 Scores on a scale Standard Deviation 1.67	-1.82 Scores on a scale Standard Deviation 1.43	-1.40 Scores on a scale Standard Deviation 2.55
Change From Baseline in Average Pain Scores by Week Week 13	-0.80 Scores on a scale Standard Deviation 1.72	-2.13 Scores on a scale Standard Deviation 2.31	-1.05 Scores on a scale Standard Deviation 1.78	-1.77 Scores on a scale Standard Deviation 1.88	-1.96 Scores on a scale Standard Deviation 1.92
Change From Baseline in Average Pain Scores by Week Week 14	-1.00 Scores on a scale Standard Deviation 1.85	-2.38 Scores on a scale Standard Deviation 2.27	-1.17 Scores on a scale Standard Deviation 1.83	-1.46 Scores on a scale Standard Deviation 1.72	-2.19 Scores on a scale Standard Deviation 1.91
Change From Baseline in Average Pain Scores by Week Week 15	-0.88 Scores on a scale Standard Deviation 1.96	-2.42 Scores on a scale Standard Deviation 2.40	-1.17 Scores on a scale Standard Deviation 1.91	-1.32 Scores on a scale Standard Deviation 2.00	-2.09 Scores on a scale Standard Deviation 1.77
Change From Baseline in Average Pain Scores by Week Week 16	-1.79 Scores on a scale Standard Deviation 1.11	-3.17 Scores on a scale Standard Deviation 2.18	-0.65 Scores on a scale Standard Deviation 1.93	-0.88 Scores on a scale Standard Deviation 1.97	-0.95 Scores on a scale Standard Deviation 1.39

SECONDARY outcome

Timeframe: Baseline and Week 15

Population: ITT Population (Modified BOCF)

The average of the last 7 available sleep scores prior to the visit, based on the 11-point Likert-type numerical rating scale for sleep interference (where 0=pain did not interfere with sleep, to 10=pain completely interfered with sleep \[unable to sleep\]), and they were reported by treatment group.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Change From Baseline to Week 15/EOT in Average Sleep Interference Scores	-0.58 Scores on a scale Standard Deviation 1.30	-0.46 Scores on a scale Standard Deviation 1.92	-1.16 Scores on a scale Standard Deviation 1.60	-0.48 Scores on a scale Standard Deviation 1.29	-0.75 Scores on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: Week 15

Population: Subset of ITT population used, including subjects that completed PGIC at Week 15 visit, and using BOCF (baseline observation carried forward) subjects that terminated prior to Week 15 received a 'No Change' if due to AE or Lack of Therapeutic Efficacy, subjects who discontinued due to other reasons used PGIC scores from Early Termination visit.

Changes were calculated using the modified BOCF method

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=20 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=42 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=20 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=19 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Patient Global Impression of Change (PGIC) at Week 15/EOT Very much improved	0 Participants	4 Participants	1 Participants	1 Participants	1 Participants
Patient Global Impression of Change (PGIC) at Week 15/EOT Much improved	3 Participants	8 Participants	4 Participants	2 Participants	1 Participants
Patient Global Impression of Change (PGIC) at Week 15/EOT Minimally improved	1 Participants	2 Participants	3 Participants	2 Participants	4 Participants
Patient Global Impression of Change (PGIC) at Week 15/EOT No change	13 Participants	27 Participants	11 Participants	13 Participants	15 Participants
Patient Global Impression of Change (PGIC) at Week 15/EOT Minimally worse	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Patient Global Impression of Change (PGIC) at Week 15/EOT Much worse	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Patient Global Impression of Change (PGIC) at Week 15/EOT Very much worse	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 15

Population: Subset of ITT population used, including subjects that completed CGIC at Week 15 visit, and using BOCF (baseline observation carried forward) subjects that terminated prior to Week 15 received a 'No Change' if due to AE or Lack of Therapeutic Efficacy, subjects who discontinued due to other reasons used CGIC scores from Early Termination visit.

Changes were calculated using the modified BOCF method

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=21 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=45 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=20 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=21 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Clinician Global Impression of Change (CGIC) at Week 15/EOT Very much improved	1 Participants	3 Participants	2 Participants	0 Participants	2 Participants
Clinician Global Impression of Change (CGIC) at Week 15/EOT Much improved	1 Participants	8 Participants	2 Participants	2 Participants	2 Participants
Clinician Global Impression of Change (CGIC) at Week 15/EOT Minimally improved	2 Participants	6 Participants	2 Participants	3 Participants	3 Participants
Clinician Global Impression of Change (CGIC) at Week 15/EOT No change	16 Participants	28 Participants	14 Participants	16 Participants	15 Participants
Clinician Global Impression of Change (CGIC) at Week 15/EOT Minimally worse	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinician Global Impression of Change (CGIC) at Week 15/EOT Much worse	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinician Global Impression of Change (CGIC) at Week 15/EOT Very much worse	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 15

Population: ITT population (Modified BOCF)

The HADS (Hospital Anxiety and Depression Scale) is a widely used, self-reported, 14-item instrument that measures the presence and severity of anxiety and depression. It consists of 2 subscales; a 7-item anxiety subscale (HADS-A) and a 7-item depression subscale (HADS-D). HADS-A consists of a 7-item scale, each scored on a 4-pt scale (0, 1, 2, or 3), where a higher score indicates worse anxiety. Range of possible HADS anxiety subscale scores is 0 to 21, and normal=(0-7), mild=(8-10), moderate=(11-14), and severe=(15-21).

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Change From Baseline to Week 15/EOT in HADS Anxiety Subscale Scores (Modified BOCF)	-0.2 Scores on a scale Standard Deviation 1.31	0.0 Scores on a scale Standard Deviation 3.25	0.1 Scores on a scale Standard Deviation 2.90	0.0 Scores on a scale Standard Deviation 1.28	-0.1 Scores on a scale Standard Deviation 2.35

SECONDARY outcome

Timeframe: Baseline and Week 15

Population: ITT population (Modified BOCF)

The HADS (Hospital Anxiety and Depression Scale) is a widely used, self-reported, 14-item instrument that measures the presence and severity of anxiety and depression. It consists of 2 subscales; a 7-item anxiety subscale (HADS-A) and a 7-item depression subscale (HADS-D). HADS-D consists of a 7-item scale, each scored on a 4-pt scale (0, 1, 2, or 3), where a higher score indicates worse depression. Range of possible HADS depression subscale scores is 0 to 21, and normal=(0-7), mild=(8-10), moderate=(11-14), and severe=(15-21).

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Change From Baseline to Week 15/EOT in HADS Depression Subscale Scores (Modified BOCF)	-0.1 Scores on a scale Standard Deviation 1.51	0.1 Scores on a scale Standard Deviation 2.11	-0.6 Scores on a scale Standard Deviation 2.28	0.2 Scores on a scale Standard Deviation 2.66	-0.3 Scores on a scale Standard Deviation 1.49

SECONDARY outcome

Timeframe: Week 15

Population: ITT population (Modified BOCF)

Allodynia is defined as a painful reaction to a non-painful stimulus.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=26 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 Participants Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 Participants Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Analysis of Allodynia (Present/Not Present) at Week 15/EOT- by Treatment Groups ITT Population (Modified BOCF) Yes	22 Participants	47 Participants	17 Participants	17 Participants	19 Participants
Analysis of Allodynia (Present/Not Present) at Week 15/EOT- by Treatment Groups ITT Population (Modified BOCF) No	4 Participants	6 Participants	5 Participants	5 Participants	4 Participants

Adverse Events

Placebo Cohort 1

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Perampanel Cohort 1, 3-week Titration

Serious events: 7 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo Cohort 2

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Perampanel Cohort 2, 1-week Titration

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Perampanel Cohort 2, 2- Week Titration

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Cohort 1 n=26 participants at risk Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 participants at risk Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 participants at risk Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 participants at risk Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 participants at risk Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Cardiac disorders Angina pectoris	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Cardiac disorders Coronary artery disease	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Peritonitis	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
General disorders Non-cardiac chest pain	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
General disorders Vestibulitis	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Infections and infestations Urinary tract infection	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Infections and infestations Pneumonia	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Injury, poisoning and procedural complications Fall	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Carotid artery occlusion	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Carotid artery stenosis	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Psychiatric disorders Mental status changes	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Renal and urinary disorders Haematuria	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.

Other adverse events

Other adverse events
Measure	Placebo Cohort 1 n=26 participants at risk Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 1, 3-week Titration n=53 participants at risk Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 3-week intervals by 2mg steps to a total of 8mg or MTD \[maximum tolerated dose\] and continued at this dose until Week 15)	Placebo Cohort 2 n=22 participants at risk Placebo (Cohort 1 and 2 differed only in timing of their scheduled visits. Cohort 1 was scheduled to visit every 3 weeks. Cohort 2 was scheduled to visit every week for the first 6 weeks and every 3 weeks thereafter)	Perampanel Cohort 2, 1-week Titration n=22 participants at risk Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 1-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)	Perampanel Cohort 2, 2- Week Titration n=23 participants at risk Perampanel 8mg (Subjects started at 2mg/day at Baseline and were up-titrated at 2-week intervals by 2mg steps to a total of 8mg or MTD and continued at this dose until Week 15)
Eye disorders Vision blurred	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Constipation	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Diarrhoea	7.7% 2/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Dyspepsia	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	13.6% 3/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Nausea	7.7% 2/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	5.7% 3/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Gastrointestinal disorders Toothache	7.7% 2/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
General disorders Fatigue	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	13.6% 3/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	8.7% 2/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
General disorders Gait disturbance	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	31.8% 7/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	8.7% 2/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Infections and infestations Nasopharyngitis	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Infections and infestations Urinary tract infection	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Injury, poisoning and procedural complications Fall	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Musculoskeletal and connective tissue disorders Muscular weakness	7.7% 2/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Balance disorder	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	8.7% 2/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Dizziness	30.8% 8/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	41.5% 22/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	54.5% 12/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	34.8% 8/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Dysarthria	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	3.8% 2/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	18.2% 4/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Headache	7.7% 2/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	7.5% 4/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	13.6% 3/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Nervous system disorders Somnolence	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	17.0% 9/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	18.2% 4/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	21.7% 5/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Psychiatric disorders Confusional state	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	13.6% 3/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Psychiatric disorders Insomnia	7.7% 2/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Skin and subcutaneous tissue disorders Rash	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	9.1% 2/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.3% 1/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	5.7% 3/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	0.00% 0/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.
Vascular disorders Hypertension	3.8% 1/26 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	1.9% 1/53 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	4.5% 1/22 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.	8.7% 2/23 • Adverse events (AEs) were collected from the time the patient signed the informed consent form until 30 days after the last dose of study drug. Safety variables included AEs, laboratory values, vital signs, and electrocardiogram measurements.

Additional Information

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Principal investigator is a sponsor employee
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