Trial Outcomes & Findings for A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs) (NCT NCT00903786)

NCT ID: NCT00903786

Last Updated: 2018-08-29

Results Overview

Safety was assessed by monitoring adverse events (AEs), adverse drug reactions, clinical laboratory parameters, vital signs, 12-lead electrocardiogram, and dependency questionnaire. AEs were graded on a 3-point scale; 1) mild: (Grade 1) discomfort noticed, but no disruption of normal daily activity, 2) moderate: (Grade 2) discomfort reduced or affected normal daily activity, and 3) severe: (Grade 3) incapacitating, with inability to work or to perform normal daily activity. AE severity associated with abnormal changes in laboratory parameters was assessed using the Ministry of Health and Welfare Notification Number 80 "Classification of Severity of Adverse Drug Reactions of Medicinal Products". TEAEs were defined as AEs that emerged during treatment (absent at pretreatment \[Baseline\]), reemerged during treatment (were present at pretreatment but stopped before treatment), or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 21 participants
• Primary outcome timeframe: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months
• Results posted on: 2018-08-29

Participant Flow

Participant milestones

Measure	Perampanel Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Overall Study STARTED	21
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Measure	Perampanel Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Overall Study Physician Decision	6
Overall Study Lack of Efficacy	5
Overall Study Reason other than lack of efficacy	4

Baseline Characteristics

A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)

Baseline characteristics by cohort

Measure	Perampanel n=21 Participants Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Age, Continuous	36.5 Years STANDARD_DEVIATION 11.02 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months

Population: The Safety Analysis Set (SAS) was defined as all participants who met the inclusion/exclusion criteria regarding "indication" (inclusion criteria number 5 of Study 231), who received at least one dose of study treatment, and who had at least one evaluable set of safety data.

Safety was assessed by monitoring adverse events (AEs), adverse drug reactions, clinical laboratory parameters, vital signs, 12-lead electrocardiogram, and dependency questionnaire. AEs were graded on a 3-point scale; 1) mild: (Grade 1) discomfort noticed, but no disruption of normal daily activity, 2) moderate: (Grade 2) discomfort reduced or affected normal daily activity, and 3) severe: (Grade 3) incapacitating, with inability to work or to perform normal daily activity. AE severity associated with abnormal changes in laboratory parameters was assessed using the Ministry of Health and Welfare Notification Number 80 "Classification of Severity of Adverse Drug Reactions of Medicinal Products". TEAEs were defined as AEs that emerged during treatment (absent at pretreatment [Baseline]), reemerged during treatment (were present at pretreatment but stopped before treatment), or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.

Outcome measures

Measure	Perampanel n=21 Participants Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel TEAEs	21 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel Treatment-related TEAEs	11 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel Serious TEAEs	5 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel TEAEs Leading to Study Treatment Dose Reduction	2 Participants

SECONDARY outcome

Timeframe: From Week 1 through Week 316 and Follow-up Period of the Extension Study, up to approximately 7 years 2 months

Population: The Efficacy Analysis Population (identical to the SAS for this study) was defined as all participants who met the inclusion/exclusion criteria regarding "indication" (inclusion criteria number 5 of Study 231), who received at least one dose of study treatment, and who had at least one data on efficacy.

Seizure frequency was derived from information (seizure count and type) recorded in the participant diary. The seizure frequency per 28 days was calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. Of the 21 participants, 20 participants concomitantly used at least 1 inducer anti-epileptic drug (AED) (carbamazepine, phenytoin, phenobarbital, or primidone), and 1 participant used only non-inducer AEDs. The data is presented as median percent change with full range.

Outcome measures

Measure	Perampanel n=21 Participants Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 9 to 16	-26.32 Percent change in seizure frequency Interval -100.0 to 31.3
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 149 to 160	-41.13 Percent change in seizure frequency Interval -100.0 to -5.1
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 1 to 4	-33.33 Percent change in seizure frequency Interval -100.0 to 24.4
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 5 to 8	-36.36 Percent change in seizure frequency Interval -100.0 to 38.9
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 17 to 28	-36.67 Percent change in seizure frequency Interval -100.0 to 15.3
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 29 to 40	-31.10 Percent change in seizure frequency Interval -100.0 to 33.3
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 41 to 52	-49.36 Percent change in seizure frequency Interval -100.0 to 5.0
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 53 to 64	-42.43 Percent change in seizure frequency Interval -100.0 to 49.7
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 65 to 76	-36.09 Percent change in seizure frequency Interval -100.0 to -1.2
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 77 to 88	-38.82 Percent change in seizure frequency Interval -100.0 to 9.8
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 89 to 100	-57.65 Percent change in seizure frequency Interval -100.0 to -9.9
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 101 to 112	-52.45 Percent change in seizure frequency Interval -100.0 to 12.5
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 113 to 124	-57.49 Percent change in seizure frequency Interval -100.0 to 28.2
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 125 to 136	-36.27 Percent change in seizure frequency Interval -100.0 to 94.4
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 137 to 148	-41.81 Percent change in seizure frequency Interval -100.0 to 23.1
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 161 to 172	-39.76 Percent change in seizure frequency Interval -100.0 to 68.9
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 173 to 184	-34.52 Percent change in seizure frequency Interval -100.0 to 29.2
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 185 to 196	-34.12 Percent change in seizure frequency Interval -100.0 to 64.1
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 197 to 208	-83.53 Percent change in seizure frequency Interval -100.0 to 22.5
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 209 to 220	-58.97 Percent change in seizure frequency Interval -100.0 to 53.3
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 221 to 232	-41.83 Percent change in seizure frequency Interval -100.0 to 86.7
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 233 to 244	-75.29 Percent change in seizure frequency Interval -100.0 to -26.5
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 245 to 256	-83.53 Percent change in seizure frequency Interval -100.0 to -2.0
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 257 to 268	-83.53 Percent change in seizure frequency Interval -100.0 to 58.5
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 269 to 280	-95.88 Percent change in seizure frequency Interval -100.0 to 19.2
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 281 to 292	-83.35 Percent change in seizure frequency Interval -100.0 to -26.5
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 293 to 304	-87.65 Percent change in seizure frequency Interval -100.0 to -5.0
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Weeks 305 to 316	-99.59 Percent change in seizure frequency Interval -100.0 to -75.3
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 Follow-up period	-8.40 Percent change in seizure frequency Interval -74.5 to 230.9

SECONDARY outcome

Timeframe: Week 1 through Week 316 and Follow-up period of the Extension study, up to approximately 7 years 2 months

Population: Efficacy Analysis Population

Responder rate (percentage of participants with greater than or equal to 50% reduction in seizure frequency for 28 days in the Treatment Period relative to that for 28 days in the observation period of Study 231 [responder]. If the reduction in seizure frequency is less than 50%, then the participants are considered as non-responders.

LOCF = Last Observation Carried Forward.

Outcome measures

Measure	Perampanel n=21 Participants Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Responder Rate During the Treatment Period-LOCF Weeks 101 to 112; Responder	50.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 125 to 136; Non-Responder	60.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 185 to 196; Non-Responder	55.6 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 221 to 232; Non-Responder	55.6 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 293 to 304; Non-Responder	16.7 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 1 to 4; Responder	42.9 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 1 to 4; Non-Responder	57.1 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 5 to 9; Responder	42.9 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 5 to 9; Non-Responder	57.1 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 9 to 16; Responder	28.6 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 9 to 16; Non-Responder	71.4 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 17 to 28; Responder	40.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 17 to 28; Non-Responder	60.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 29 to 40; Responder	44.4 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 29 to 40; Non-Responder	55.6 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 41 to 52; Responder	47.1 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 41 to 52; Non-Responder	52.9 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 53 to 64; Responder	41.2 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 53 to 64; Non-Responder	58.8 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 65 to 76; Responder	41.2 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 65 to 76; Non-Responder	58.8 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 77 to 88; Responder	31.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 77 to 88; Non-Responder	68.8 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 89 to 100; Responder	56.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 89 to 100; Non-Responder	43.8 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 101 to 112; Non-Responder	50.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 113 to 124; Responder	56.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 113 to 124; Non-Responder	43.8 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 125 to 136; Responder	40.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 137 to 148; Responder	38.5 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 137 to 148; Non-Responder	61.5 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 149 to 160; Responder	50.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 149 to 160; Non- Responder	50.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 161 to 172; Responder	40.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 161 to 172; Non-Responder	60.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 173 to 184; Responder	40.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 173 to 184; Non-Responder	60.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 185 to 196; Responder	44.4 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 197 to 208; Responder	66.7 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 197 to 208; Non-Responder	33.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 209 to 220; Responder	55.6 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 209 to 220; Non-Responder	44.4 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 221 to 232; Responder	44.4 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 233 to 244; Responder	57.1 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 233 to 244; Non-Responder	42.9 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 245 to 256; Responder	85.7 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 245 to 256; Non-Responder	14.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 257 to 268; Responder	85.7 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 257 to 268; Non-Responder	14.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 269 to 280; Responder	83.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 269-280; Non-Responder	16.7 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 281 to 292; Responder	83.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 281 to 292; Non-Responder	16.7 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 293 to 304; Responder	83.3 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 305 to 316; Responder	100.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Weeks 305 to 316; Non-Responder	0.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Follow-up period; Responder	20.0 Percentage of participants
Responder Rate During the Treatment Period-LOCF Follow-up period; Non-responder	80.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 52 and End of Treatment; up to approximately 7 years 2 months

Population: Efficacy Analysis Population

Each participant evaluated him/herself for PGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing seizure conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.

Outcome measures

Measure	Perampanel n=21 Participants Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Minimally improved; Week 52	52.9 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Much worse; Week 52	0.0 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Very much improved; End of Treatment	14.3 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Much improved; End of Treatment	14.3 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment No change; Week 52	11.8 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Minimally worse; Week 52	0.0 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Very much worse; Week 52	0.0 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Minimally improved; End of Treatment	28.6 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment No change; End of Treatment	38.1 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Minimally worse; End of Treatment	4.8 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Much worse; End of Treatment	0.0 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Very much worse; End of Treatment	0.0 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Very much improved; Week 52	17.6 Percentage of participants
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment Much improved; Week 52	17.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 52 and End of Treatment, up to approximately 7 years 2 months

Population: Efficacy Analysis Population

The investigator evaluated each participant for CGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing medical conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.

Outcome measures

Measure	Perampanel n=21 Participants Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Minimally improved; Week 52	64.7 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Minimally worse; Week 52	0.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Much worse; Week 52	0.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Very much worse; Week 52	0.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Much improved; End of Treatment	9.5 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Minimally improved; End of Treatment	19.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment No change; End of Treatment	61.9 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Minimally worse; End of Treatment	0.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Much worse; End of Treatment	0.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Very much worse; End of Treatment	0.0 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment No change; Week 52	17.6 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Very much improved; End of Treatment	9.5 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Very much improved; Week 52	11.8 Percentage of participants
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment Much improved; Week 52	5.9 Percentage of participants

Adverse Events

Perampanel

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Perampanel n=21 participants at risk Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Infections and infestations Pneumonia bacterial	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Epilepsy	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Gastric ulcer	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Haemorrhoids	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Joint dislocation	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.

Other adverse events

Measure	Perampanel n=21 participants at risk Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) \[NCT00849212\]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Infections and infestations Nasopharyngitis	66.7% 14/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Gingivitis	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Influenza	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Gastroenteritis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Herpes zoster	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Hordeolum	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Pharyngitis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Urinary tract infection	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Infections and infestations Pneumonia bacterial	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Blood and lymphatic system disorders Iron deficiency anaemia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Metabolism and nutrition disorders Hyperuricaemia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Metabolism and nutrition disorders Hyperlipidaemia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Metabolism and nutrition disorders Type 2 diabetes mellitus	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Psychiatric disorders Anxiety	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Psychiatric disorders Depression	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Psychiatric disorders Insomnia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Psychiatric disorders Mental status changes	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Dizziness	28.6% 6/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Somnolence	28.6% 6/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Headache	19.0% 4/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Tremor	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Ataxia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Epilepsy	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Nervous system disorders Partial seizures with secondary generalisation	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Eye disorders Conjunctivitis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Eye disorders Diplopia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Eye disorders Presbyopia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Eye disorders Visual acuity reduced	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Eye disorders Vitreous floaters	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	19.0% 4/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Respiratory, thoracic and mediastinal disorders Cough	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Dental caries	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Gastritis	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Nausea	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Stomatitis	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Abdominal pain upper	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Gastric ulcer	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Haemorrhoids	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Hiatus hernia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Mouth haemorrhage	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Gastrointestinal disorders Oesophagitis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Hepatobiliary disorders Hepatic function abnormal	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Acne	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Dermatitis contact	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Drug eruption	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Eczema	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Eczema asteatotic	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Hypohidrosis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Skin fissures	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Skin and subcutaneous tissue disorders Urticaria	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Musculoskeletal and connective tissue disorders Back pain	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Musculoskeletal and connective tissue disorders Arthritis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Musculoskeletal and connective tissue disorders Myalgia	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Musculoskeletal and connective tissue disorders Tenosynovitis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Renal and urinary disorders Renal impairment	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Reproductive system and breast disorders Prostatitis	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Malaise	14.3% 3/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Pyrexia	14.3% 3/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Irritability	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Feeling abnormal	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Feeling drunk	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Local swelling	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
General disorders Thirst	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Gamma-glutamyltransferase increased	14.3% 3/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Blood glucose increased	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Blood calcium decreased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Blood creatine phosphokinase increased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Blood creatinine increased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Blood glucose decreased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Blood pressure increased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Eosinophil count increased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Glucose urine present	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Protein urine present	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Investigations Human chorionic gonadotropin increased	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Contusion	57.1% 12/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Laceration	19.0% 4/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Fall	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Rib fracture	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Mouth injury	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Excoriation	9.5% 2/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Chillblains	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Foot fracture	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Hand fracture	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Joint dislocation	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Ligament sprain	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Patella fracture	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Thermal burn	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Tongue injury	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Ligament injury	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.
Injury, poisoning and procedural complications Lower limb fracture	4.8% 1/21 • From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months Treatment-emergent adverse events were defined as adverse events (AE) that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug, worsened in severity. AE severity was graded using Ministry of Health and Welfare Notification Number 80 Classification of Severity of Adverse Drug Reactions of Medicinal Products.

Additional Information

Eisai Medical Services Inc.

Eisai Inc.

Phone: 1-888-422-4743

Email: esi_medinfo@eisai.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER