Trial Outcomes & Findings for Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome (NCT NCT02834793)

NCT ID: NCT02834793

Last Updated: 2022-03-09

Results Overview

Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 101 participants
• Primary outcome timeframe: Baseline up to 18 weeks
• Results posted on: 2022-03-09

Participant Flow

Participants took part in the study at 40 investigative sites in Australia, Belgium, the Czech Republic, Japan, India, South Korea, and the United States from 13 December 2016 to 19 July 2021. A total of 101 participants were enrolled (signed informed consent) and 70 participants were randomized to receive study treatment in Core Study Phase.

This study included a Core Study Phase and an Extension Phase, which in turn consisted of Extension A and Extension B. Study was terminated early by the sponsor due to recruitment challenges that were further impacted by the COVID-19 pandemic.

Participant milestones

Measure	Core Study Phase: Placebo Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel Participants received starting dose of perampanel, one 2 milligram (mg) oral tablet or 4 milliliter (mL) oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 milligram per day (mg/day) during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase A: Perampanel Participants who completed the Core Study Phase and who were eligible entered into Extension Phase A. Participants previously assigned to perampanel arm (Core Study Phase) continued taking study medication at the dose received during the Core maintenance period, and participants previously assigned to a placebo arm (Core Study Phase) started perampanel dose as one 2 mg tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to a maximum dose of 8 mg/day for 6 weeks conversion period of Extension Phase A. After the conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during the maintenance period (46 weeks) of Extension Phase A as per the investigator's discretion. The total duration of the conversion period and maintenance period in Extension Phase A was 52 weeks.	Extension Phase B: Perampanel Participants who completed Extension Phase A and who were eligible entered into Extension Phase B. Participants received perampanel at their optimal perampanel dose (that is, dose maintained at the end of Extension A) until perampanel was available commercially or accessible via extended access program (EAP) (in the country in which a participant resides) or unless study termination by the sponsor (up to 188 weeks).
Core Study (Up to 18 Weeks) STARTED	36	34	0	0
Core Study (Up to 18 Weeks) COMPLETED	32	29	0	0
Core Study (Up to 18 Weeks) NOT COMPLETED	4	5	0	0
Extension Phase A (up to 52 Weeks) STARTED	0	0	58	0
Extension Phase A (up to 52 Weeks) COMPLETED	0	0	32	0
Extension Phase A (up to 52 Weeks) NOT COMPLETED	0	0	26	0
Extension Phase B (up to 188 Weeks) STARTED	0	0	0	13
Extension Phase B (up to 188 Weeks) COMPLETED	0	0	0	1
Extension Phase B (up to 188 Weeks) NOT COMPLETED	0	0	0	12

Reasons for withdrawal

Measure	Core Study Phase: Placebo Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel Participants received starting dose of perampanel, one 2 milligram (mg) oral tablet or 4 milliliter (mL) oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 milligram per day (mg/day) during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase A: Perampanel Participants who completed the Core Study Phase and who were eligible entered into Extension Phase A. Participants previously assigned to perampanel arm (Core Study Phase) continued taking study medication at the dose received during the Core maintenance period, and participants previously assigned to a placebo arm (Core Study Phase) started perampanel dose as one 2 mg tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to a maximum dose of 8 mg/day for 6 weeks conversion period of Extension Phase A. After the conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during the maintenance period (46 weeks) of Extension Phase A as per the investigator's discretion. The total duration of the conversion period and maintenance period in Extension Phase A was 52 weeks.	Extension Phase B: Perampanel Participants who completed Extension Phase A and who were eligible entered into Extension Phase B. Participants received perampanel at their optimal perampanel dose (that is, dose maintained at the end of Extension A) until perampanel was available commercially or accessible via extended access program (EAP) (in the country in which a participant resides) or unless study termination by the sponsor (up to 188 weeks).
Core Study (Up to 18 Weeks) Withdrawal by Subject	2	1	0	0
Core Study (Up to 18 Weeks) Lack of Efficacy	1	0	0	0
Core Study (Up to 18 Weeks) Lost to Follow-up	1	0	0	0
Core Study (Up to 18 Weeks) Adverse Event	0	3	0	0
Core Study (Up to 18 Weeks) Study terminated by sponsor	0	1	0	0
Extension Phase A (up to 52 Weeks) Withdrawal by Subject	0	0	7	0
Extension Phase A (up to 52 Weeks) Lack of Efficacy	0	0	4	0
Extension Phase A (up to 52 Weeks) Adverse Event	0	0	5	0
Extension Phase A (up to 52 Weeks) Study terminated by sponsor	0	0	9	0
Extension Phase A (up to 52 Weeks) Other	0	0	1	0
Extension Phase B (up to 188 Weeks) Lack of Efficacy	0	0	0	1
Extension Phase B (up to 188 Weeks) Adverse Event	0	0	0	1
Extension Phase B (up to 188 Weeks) Study terminated by sponsor	0	0	0	8
Extension Phase B (up to 188 Weeks) Other	0	0	0	1
Extension Phase B (up to 188 Weeks) Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome

Baseline characteristics by cohort

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Total n=70 Participants Total of all reporting groups
Age, Continuous	13.3 years STANDARD_DEVIATION 7.80 • n=5 Participants	14.7 years STANDARD_DEVIATION 10.37 • n=7 Participants	14.0 years STANDARD_DEVIATION 9.10 • n=5 Participants
Age, Customized In utero	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Preterm newborn infants (gestational age < 37 wks)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Newborns (0-27 days)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Infants and toddlers (28 days-23 months)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Children (2-11 years)	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Age, Customized Adolescents (12-17 years)	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Age, Customized Adults (18-64 years)	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Age, Customized From 65-84 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized 85 years and over	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	17 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	30 Participants n=7 Participants	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 18 weeks

Population: The full analysis set (FAS) was the group of randomized participants who received at least one dose of the study drug and had at least one post-dose seizure measurement.

Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)	-4.51 percent change Interval -86.2 to 201.8	-23.07 percent change Interval -96.4 to 371.4	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of the study drug and had at least one post-dose seizure measurement.

Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries were used to collect seizure counts and types. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)	-6.53 percent change Interval -63.6 to 266.8	-18.23 percent change Interval -96.9 to 103.5	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of the study drug and had at least one post-dose seizure measurement.

Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. A responder was a participant who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures	25.0 percentage of participants	44.1 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of study drug and had at least one post-dose seizure measurement.

Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a participant who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Total Seizures	16.7 percentage of participants	32.4 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of study drug and had at least one post-dose seizure measurement. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or could lead to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.

Outcome measures

Measure	Core Study Phase: Placebo n=30 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=27 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Median Percent Change in Non-drop Seizure Frequency Per 28 Days During Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline)	-13.21 percent change Interval -100.0 to 2288.1	-12.33 percent change Interval -98.7 to 63.2	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of the study drug and had at least one post-dose seizure measurement. Here "number analyzed" were participants who were evaluable for the outcome measure at given categories.

Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries were used to collect seizure counts and types. A responder was a participant who experienced a 75% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Percentage of Participants With 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures Total Seizures	0 percentage of participants	11.8 percentage of participants	—
Core Study Phase: Percentage of Participants With 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures Non-drop Seizures	10.0 percentage of participants	18.5 percentage of participants	—
Core Study Phase: Percentage of Participants With 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures Drop Seizures	13.9 percentage of participants	26.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of the study drug and had at least one post-dose seizure measurement. Here "number analyzed" were participants who were evaluable for the outcome measure at given categories.

Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a participant who experienced a 100% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Percentage of Participants With 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures Drop Seizure	0 percentage of participants	2.9 percentage of participants	—
Core Study Phase: Percentage of Participants With 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures Non-drop Seizure	6.5 percentage of participants	3.6 percentage of participants	—
Core Study Phase: Percentage of Participants With 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures Total Seizures	0 percentage of participants	2.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of the study drug and had at least one post-dose seizure measurement. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or could lead to a fall or injury, depending on the participant's position at the time of the attack or spell. A responder was a participant who experienced a 50% or greater reduction in non-drop seizure frequency per 28 days during Maintenance from prerandomization.

Outcome measures

Measure	Core Study Phase: Placebo n=30 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=27 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Non-drop Seizures	16.7 percentage of participants	44.4 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to 18 weeks

Population: The FAS was the group of randomized participants who received at least one dose of study drug and had at least one post-dose seizure measurement. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Assessment of disease severity utilized the CGIC scale at end of treatment to evaluate participants change in disease status from baseline. The CGIC is a 7-point likert scale that measures a physician's global impression of a participants clinical condition. Scale ranged from 1 to 7 with lower score indicated improvement (1=very much improved, 2=much improved, 3=minimally improved), higher score indicated worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicated no change.

Outcome measures

Measure	Core Study Phase: Placebo n=35 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=32 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase Much worse	2.9 percentage of participants	9.4 percentage of participants	—
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase Very much worse	0 percentage of participants	0 percentage of participants	—
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase Very much improved	0 percentage of participants	9.4 percentage of participants	—
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase Much improved	8.6 percentage of participants	15.6 percentage of participants	—
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase Minimally improved	25.7 percentage of participants	18.8 percentage of participants	—
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase No change	57.1 percentage of participants	34.4 percentage of participants	—
Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase Minimally worse	5.7 percentage of participants	12.5 percentage of participants	—

SECONDARY outcome

Timeframe: From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)

Population: SAS was group of participants who received at least one dose of study drug and had at least one post-dose safety assessment. As per the planned safety analysis, safety data for Extension A and Extension B was reported together as 'Extension Phase' arm.

A TEAE was defined as an adverse event with an onset date, or a worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to 28 days following study drug discontinuation. An AE was defined as any untoward medical occurrence in a participant or clinical investigation in a participant administered an investigational product. An AE does not necessarily have a causal relationship with a medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel n=58 Participants Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	26 Participants	29 Participants	50 Participants
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	6 Participants	11 Participants

SECONDARY outcome

Timeframe: From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)

Population: SAS was group of participants who received at least one dose of study drug and had at least one post-dose safety assessment. As per the planned safety analysis, safety data for Extension A and Extension B was reported together as 'Extension Phase' arm.

Treatment-emergent markedly abnormal value for laboratory values was based Common Terminology Criteria for Adverse events (CTCAE) Version 4.0, and determined as if the post baseline CTCAE Version 4.0 grade increases from baseline and the post baseline grade was >=2 (>=3 for phosphate). Laboratory tests included: Hematology count with differential, Chemistry (Electrolytes, Liver function tests, Renal function parameters, Other: albumin, calcium, cholesterol, globulin, glucose, lactate dehydrogenase, phosphorus, total protein, lipid panel, uric acid), Urinalysis, and Viral tests (Hepatitis B surface antigen, Hepatitis C).

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel n=58 Participants Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Platelets	1 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal High: Sodium	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Albumin	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal High: Cholesterol	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal High: Triglycerides	2 Participants	1 Participants	4 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Haemoglobin	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Lymphocytes	0 Participants	0 Participants	2 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Glucose	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal High: Alkaline Phosphatase	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Neutrophils	0 Participants	1 Participants	7 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal High: Gamma Glutamyl Transferase	1 Participants	1 Participants	2 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Bicarbonate	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal Low: Leukocytes	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Markedly Abnormal High: Alanine Aminotransferase	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)

Population: SAS was group of participants who received at least one dose of the study drug and had at least one post-dose safety assessment. As per the planned safety analysis, safety data for Extension A and Extension B was reported together as 'Extension Phase' arm.

Clinically significant means that a value must have met both the criterion value and satisfied the magnitude of change relative to baseline. Vital sign parameters included systolic blood pressure (BP), diastolic BP, pulse rate.

Outcome measures

Measure	Core Study Phase: Placebo n=36 Participants Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 Participants Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel n=58 Participants Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period, and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Number of Participants With Clinically Significant Vital Signs Systolic Blood Pressure: Low	4 Participants	2 Participants	7 Participants
Number of Participants With Clinically Significant Vital Signs Systolic Blood Pressure: High	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Vital Signs Diastolic Blood Pressure: Low	5 Participants	1 Participants	13 Participants
Number of Participants With Clinically Significant Vital Signs Pulse Rate: High	4 Participants	5 Participants	11 Participants
Number of Participants With Clinically Significant Vital Signs Diastolic Blood Pressure: High	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Vital Signs Pulse Rate: Low	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Week 18

Population: The PK analysis set was the group of participants who received perampanel or placebo who had seizure frequency data with documented dosing history. As population PK and PK/PD analysis were not conducted, therefore data was not collected and analyzed.

Due to the early termination of the study resulting in reduced sample size and the variability in treatment response, population pharmacokinetic (PK) analysis and population pharmacokinetic/pharmacodynamic (PK/PD) modeling planned for this study were not conducted and hence data was not collected and analyzed for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Core Study Phase: Placebo

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Core Study Phase: Perampanel

Serious events: 6 serious events

Other events: 29 other events

Deaths: 0 deaths

Extension Phase: Perampanel

Serious events: 11 serious events

Other events: 50 other events

Deaths: 2 deaths

Serious adverse events

Measure	Core Study Phase: Placebo n=36 participants at risk Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 participants at risk Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel n=58 participants at risk Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period; and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Gastrointestinal disorders Gastrointestinal haemorrhage	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/58 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Vomiting	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Pneumonia	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Metabolism and nutrition disorders Dehydration	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/58 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Epilepsy	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/58 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Seizure	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Psychiatric disorders Mental status changes	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Respiratory, thoracic and mediastinal disorders Asthma	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/58 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/58 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Blood and lymphatic system disorders Cytogenetic abnormality	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Dental caries	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Haematemesis	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
General disorders Sudden unexplained death in epilepsy	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Bronchitis	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Infected skin ulcer	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Influenza	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Lower respiratory tract infection viral	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Sepsis	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Lethargy	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Quadriplegia	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Seizure cluster	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	1.7% 1/58 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.

Other adverse events

Measure	Core Study Phase: Placebo n=36 participants at risk Participants received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension, once daily at bedtime during the titration period. During the maintenance period, participants continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study Phase was 18 weeks.	Core Study Phase: Perampanel n=34 participants at risk Participants received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, participants continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study Phase was 18 weeks.	Extension Phase: Perampanel n=58 participants at risk Participants who completed Core Study and who were eligible entered Extension A. Participants who received perampanel in Core Study, continued at dose received during Core maintenance period; and participants who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, participants could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator's discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Participants who completed Extension A and who were eligible entered into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose (dose at end of Extension A) until perampanel was available commercially or unless study termination (up to 188 weeks).
Gastrointestinal disorders Constipation	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	10.3% 6/58 • Number of events 6 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Diarrhoea	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Nausea	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Gastrointestinal disorders Vomiting	13.9% 5/36 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Bronchitis	8.3% 3/36 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Hordeolum	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Influenza	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Nasopharyngitis	5.6% 2/36 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	12.1% 7/58 • Number of events 15 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Pneumonia	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Infections and infestations Upper respiratory tract infection	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	11.8% 4/34 • Number of events 7 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	12.1% 7/58 • Number of events 11 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Injury, poisoning and procedural complications Skin laceration	2.8% 1/36 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Investigations Weight increased	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	10.3% 6/58 • Number of events 6 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Balance disorder	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.6% 5/58 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Drooling	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.6% 5/58 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Lethargy	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Sedation	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Somnolence	5.6% 2/36 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	23.5% 8/34 • Number of events 8 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	19.0% 11/58 • Number of events 12 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Psychiatric disorders Agitation	5.6% 2/36 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Psychiatric disorders Irritability	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	14.7% 5/34 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	12.1% 7/58 • Number of events 8 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 2/36 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Skin and subcutaneous tissue disorders Rash	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	6.9% 4/58 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
General disorders Fatigue	2.8% 1/36 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	6.9% 4/58 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
General disorders Gait disturbance	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	8.8% 3/34 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	6.9% 4/58 • Number of events 6 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
General disorders Peripheral swelling	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.9% 2/34 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	3.4% 2/58 • Number of events 2 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
General disorders Pyrexia	13.9% 5/36 • Number of events 5 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	2.9% 1/34 • Number of events 1 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	13.8% 8/58 • Number of events 9 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Injury, poisoning and procedural complications Contusion	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Ataxia	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Dizziness	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Nervous system disorders Seizure	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Psychiatric disorders Aggression	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	6.9% 4/58 • Number of events 4 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
Psychiatric disorders Insomnia	0.00% 0/36 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	0.00% 0/34 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.	5.2% 3/58 • Number of events 3 • From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks) Participants received varying doses in Extension Phase depending on tolerance. Participants were titrated up to 12 mg/day, hence AEs were summarized as a single arm for Extension Phase. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.

Additional Information

Eisai Medical Information

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