Trial Outcomes & Findings for DS-5565 Phase III Study for Post-herpetic Neuralgia (NCT NCT02318719)

Last Updated: 2020-11-02

Results Overview

Each participant recorded a pain score in the electronic patient diary once daily from the day after the screening visit (Visit 1) to the end of treatment/early termination visit (Visit 10). Prior to taking the study drug each morning, the participant selected the number that best described his or her pain over the past 24 hours on a scale of 0 (no pain) to 10 (worst possible pain). Higher ADPS scores indicated worse outcome. ADPS was the weekly average pain score based on the pain scores from the electronic patient diaries (Pain diary). In this outcome, the change from baseline in ADPS is being reported with negative values representing improvements in average daily pain. The larger the negative value (ie. improvement), the greater the improvement in average daily pain.

Recruitment status

COMPLETED

Study phase

Target enrollment

765 participants

Primary outcome timeframe

Baseline to Week 14

Results posted on

2020-11-02

Participant Flow

A total of 765 participants who met all inclusion and no exclusion criteria were enrolled in the study; 763 participants received treatment in the double-blind phase. A total of 239 participants received treatment in the open-label extension phase.

This study included a double-blind phase where participants received DS-5565 (15 mg, 20 mg, or 30 mg) or placebo and an open-label extension phase where participants received DS-5565 (starting dose 5 mg).

Participant milestones

Participant milestones
Measure	Placebo Participants who received placebo for 14 weeks.	DS-5565 15 mg/Day Participants received oral administrations of DS-5565 15 mg/day with a 2 week titration (5 mg/day during 1st week and 10 mg/day during 2nd week) followed by 12 weeks fixed dose (15 mg/day).	DS-5565 20 mg/Day Participants received oral administrations of DS-5565 20 mg/day with a 1 week titration (5 mg BID) followed by 13 weeks fixed dose (10 mg BID).	DS-5565 30 mg/Day Participants received oral administrations of DS-5565 30 mg/day with a 2 week titration (5 mg BID during 1st week and 10 mg BID during 2nd week) followed by 12 weeks fixed dose (15 mg BID).	DS-5565 Open-label Extension Participants who received 5 mg BID for the first 2 weeks and 10 mg BID for the second 2 weeks (i.e., Week 3 and 4). At Week 5, the dosage escalated to 15 mg BID if there were no concerns in safety. For the subsequent visits, the dosage may have changed to either 10 mg BID or 15 mg BID depending on safety findings.
Double-blind Phase STARTED	304	153	153	155	0
Double-blind Phase Did Not Receive Treatment	1	1	0	0	0
Double-blind Phase COMPLETED	266	137	128	140	0
Double-blind Phase NOT COMPLETED	38	16	25	15	0
Open-label Extension Phase STARTED	0	0	0	0	239
Open-label Extension Phase COMPLETED	0	0	0	0	184
Open-label Extension Phase NOT COMPLETED	0	0	0	0	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants who received placebo for 14 weeks.	DS-5565 15 mg/Day Participants received oral administrations of DS-5565 15 mg/day with a 2 week titration (5 mg/day during 1st week and 10 mg/day during 2nd week) followed by 12 weeks fixed dose (15 mg/day).	DS-5565 20 mg/Day Participants received oral administrations of DS-5565 20 mg/day with a 1 week titration (5 mg BID) followed by 13 weeks fixed dose (10 mg BID).	DS-5565 30 mg/Day Participants received oral administrations of DS-5565 30 mg/day with a 2 week titration (5 mg BID during 1st week and 10 mg BID during 2nd week) followed by 12 weeks fixed dose (15 mg BID).	DS-5565 Open-label Extension Participants who received 5 mg BID for the first 2 weeks and 10 mg BID for the second 2 weeks (i.e., Week 3 and 4). At Week 5, the dosage escalated to 15 mg BID if there were no concerns in safety. For the subsequent visits, the dosage may have changed to either 10 mg BID or 15 mg BID depending on safety findings.
Double-blind Phase Adverse Event	7	6	12	4	0
Double-blind Phase Lack of Efficacy	5	0	1	1	0
Double-blind Phase Protocol Violation	0	1	3	0	0
Double-blind Phase Withdrawal by Subject	25	7	9	10	0
Double-blind Phase Other	1	2	0	0	0
Open-label Extension Phase Adverse Event	0	0	0	0	15
Open-label Extension Phase Death	0	0	0	0	1
Open-label Extension Phase Lack of Efficacy	0	0	0	0	1
Open-label Extension Phase Withdrawal by Subject	0	0	0	0	31
Open-label Extension Phase Other	0	0	0	0	7

Baseline Characteristics

DS-5565 Phase III Study for Post-herpetic Neuralgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=304 Participants Participants who received placebo for 14 weeks.	DS-5565 15 mg n=153 Participants Participants who received oral administration of DS-5565 15 mg with a 2 week titration and 12 weeks fixed dose treatment period.	DS-5565 20 mg n=153 Participants Participants who received oral administration of DS-5565 20 mg with a 1 week titration and 13 weeks fixed dose treatment period.	DS-5565 30 mg n=155 Participants Participants who received oral administration of DS-5565 30 mg with a 2 week titration and 12 weeks fixed dose treatment period.	Total n=765 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	102 Participants n=5 Participants	47 Participants n=7 Participants	39 Participants n=5 Participants	64 Participants n=4 Participants	252 Participants n=21 Participants
Age, Categorical >=65 years	202 Participants n=5 Participants	106 Participants n=7 Participants	114 Participants n=5 Participants	91 Participants n=4 Participants	513 Participants n=21 Participants
Age, Continuous	66.2 years STANDARD_DEVIATION 10.13 • n=5 Participants	66.6 years STANDARD_DEVIATION 8.97 • n=7 Participants	68.9 years STANDARD_DEVIATION 9.19 • n=5 Participants	64.5 years STANDARD_DEVIATION 10.74 • n=4 Participants	66.5 years STANDARD_DEVIATION 9.94 • n=21 Participants
Sex: Female, Male Female	127 Participants n=5 Participants	56 Participants n=7 Participants	62 Participants n=5 Participants	59 Participants n=4 Participants	304 Participants n=21 Participants
Sex: Female, Male Male	177 Participants n=5 Participants	97 Participants n=7 Participants	91 Participants n=5 Participants	96 Participants n=4 Participants	461 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	304 Participants n=5 Participants	153 Participants n=7 Participants	153 Participants n=5 Participants	155 Participants n=4 Participants	765 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Japan	304 participants n=5 Participants	153 participants n=7 Participants	153 participants n=5 Participants	155 participants n=4 Participants	765 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Week 14

Population: Average daily pain score (ADPS) was assessed in the modified Intent-to-Treat Analysis Set.

Outcome measures

Outcome measures
Measure	Placebo n=303 Participants Participants who received placebo for 14 weeks.	DS-5565 15 mg/Day n=152 Participants Participants received oral administrations of DS-5565 15 mg/day with a 2 week titration (5 mg/day during 1st week and 10 mg/day during 2nd week) followed by 12 weeks fixed dose (15 mg/day).	DS-5565 20 mg/Day n=153 Participants Participants received oral administrations of DS-5565 20 mg/day with a 1 week titration (5 mg BID) followed by 13 weeks fixed dose (10 mg BID).	DS-5565 30 mg/Day n=155 Participants Participants received oral administrations of DS-5565 30 mg/day with a 2 week titration (5 mg BID during 1st week and 10 mg BID during 2nd week) followed by 12 weeks fixed dose (15 mg BID).
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 1	-0.10 units on a scale Standard Deviation 0.743	-0.39 units on a scale Standard Deviation 0.787	-0.54 units on a scale Standard Deviation 0.783	-0.46 units on a scale Standard Deviation 0.693
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 2	-0.33 units on a scale Standard Deviation 0.902	-0.72 units on a scale Standard Deviation 1.036	-1.06 units on a scale Standard Deviation 0.998	-0.95 units on a scale Standard Deviation 1.003
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 3	-0.48 units on a scale Standard Deviation 1.030	-0.96 units on a scale Standard Deviation 1.195	-1.16 units on a scale Standard Deviation 1.122	-1.20 units on a scale Standard Deviation 1.188
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 4	-0.64 units on a scale Standard Deviation 1.163	-1.08 units on a scale Standard Deviation 1.283	-1.24 units on a scale Standard Deviation 1.192	-1.33 units on a scale Standard Deviation 1.236
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 5	-0.74 units on a scale Standard Deviation 1.215	-1.17 units on a scale Standard Deviation 1.351	-1.36 units on a scale Standard Deviation 1.233	-1.49 units on a scale Standard Deviation 1.275
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 6	-0.81 units on a scale Standard Deviation 1.329	-1.29 units on a scale Standard Deviation 1.412	-1.44 units on a scale Standard Deviation 1.337	-1.55 units on a scale Standard Deviation 1.277
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 7	-0.96 units on a scale Standard Deviation 1.399	-1.32 units on a scale Standard Deviation 1.409	-1.45 units on a scale Standard Deviation 1.382	-1.67 units on a scale Standard Deviation 1.346
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 8	-1.03 units on a scale Standard Deviation 1.466	-1.39 units on a scale Standard Deviation 1.509	-1.40 units on a scale Standard Deviation 1.455	-1.62 units on a scale Standard Deviation 1.375
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 9	-1.09 units on a scale Standard Deviation 1.478	-1.44 units on a scale Standard Deviation 1.574	-1.42 units on a scale Standard Deviation 1.480	-1.72 units on a scale Standard Deviation 1.431
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 10	-1.15 units on a scale Standard Deviation 1.547	-1.49 units on a scale Standard Deviation 1.632	-1.51 units on a scale Standard Deviation 1.564	-1.81 units on a scale Standard Deviation 1.486
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 11	-1.22 units on a scale Standard Deviation 1.601	-1.53 units on a scale Standard Deviation 1.647	-1.60 units on a scale Standard Deviation 1.576	-1.84 units on a scale Standard Deviation 1.473
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 12	-1.21 units on a scale Standard Deviation 1.614	-1.59 units on a scale Standard Deviation 1.727	-1.63 units on a scale Standard Deviation 1.624	-1.89 units on a scale Standard Deviation 1.519
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 13	-1.25 units on a scale Standard Deviation 1.665	-1.63 units on a scale Standard Deviation 1.769	-1.68 units on a scale Standard Deviation 1.643	-1.95 units on a scale Standard Deviation 1.486
Change in the Average Daily Pain Score (ADPS) From Baseline to Week 14 Following Oral Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 14	-1.31 units on a scale Standard Deviation 1.710	-1.67 units on a scale Standard Deviation 1.717	-1.73 units on a scale Standard Deviation 1.715	-1.96 units on a scale Standard Deviation 1.501

SECONDARY outcome

Timeframe: From baseline (Week 14) to Week 66

Population: Visual analog scale (VAS) was assessed in the modified Intent-to-Treat Analysis Set.

Visual Analog Scale (VAS) pain is a 10-point assessment tool to measure pain levels, where 0 is defined as 'no pain' and 10 is defined as 'worst possible pain'. Higher VAS pain scores indicate worse outcome. In this outcome, the change from baseline in VAS pain is being reported with negative values representing improvements in pain intensity. The larger the negative value (ie. improvement), the greater the improvement in pain intensity.

Outcome measures

Outcome measures
Measure	Placebo n=237 Participants Participants who received placebo for 14 weeks.	DS-5565 15 mg/Day Participants received oral administrations of DS-5565 15 mg/day with a 2 week titration (5 mg/day during 1st week and 10 mg/day during 2nd week) followed by 12 weeks fixed dose (15 mg/day).	DS-5565 20 mg/Day Participants received oral administrations of DS-5565 20 mg/day with a 1 week titration (5 mg BID) followed by 13 weeks fixed dose (10 mg BID).	DS-5565 30 mg/Day Participants received oral administrations of DS-5565 30 mg/day with a 2 week titration (5 mg BID during 1st week and 10 mg BID during 2nd week) followed by 12 weeks fixed dose (15 mg BID).
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 16	-0.70 units on a scale Standard Deviation 9.530	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 18	4.60 units on a scale Standard Deviation 9.850	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 22	-8.30 units on a scale Standard Deviation 12.070	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 26	-8.60 units on a scale Standard Deviation 12.030	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 30	-8.70 units on a scale Standard Deviation 13.670	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 34	-10.00 units on a scale Standard Deviation 14.260	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 38	-10.40 units on a scale Standard Deviation 14.450	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 42	-11.20 units on a scale Standard Deviation 13.930	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 46	-12.00 units on a scale Standard Deviation 13.890	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 50	-12.60 units on a scale Standard Deviation 14.530	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 54	-12.50 units on a scale Standard Deviation 14.760	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 58	-12.90 units on a scale Standard Deviation 15.250	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 62	-14.00 units on a scale Standard Deviation 16.790	—	—	—
Change in Visual Analog Scale (VAS) Pain From Baseline (Week 14) to Week 66 Following Administration of DS-5565 in Asian Participants With Post-herpetic Neuralgia Week 66	-14.70 units on a scale Standard Deviation 15.270	—	—	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

DS-5565 15 mg/Day

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

DS-5565 20 mg/Day

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

DS-5565 30 mg/Day

Serious events: 0 serious events

Other events: 72 other events

Deaths: 0 deaths

DS-5565 Open-label Extension

Serious events: 20 serious events

Other events: 99 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=303 participants at risk Participants who received placebo for 14 weeks.	DS-5565 15 mg/Day n=152 participants at risk Participants received oral administrations of DS-5565 15 mg/day with a 2 week titration (5 mg/day during 1st week and 10 mg/day during 2nd week) followed by 12 weeks fixed dose (15 mg/day).	DS-5565 20 mg/Day n=153 participants at risk Participants received oral administrations of DS-5565 20 mg/day with a 1 week titration (5 mg BID) followed by 13 weeks fixed dose (10 mg BID).	DS-5565 30 mg/Day n=155 participants at risk Participants received oral administrations of DS-5565 30 mg/day with a 2 week titration (5 mg BID during 1st week and 10 mg BID during 2nd week) followed by 12 weeks fixed dose (15 mg BID).	DS-5565 Open-label Extension n=237 participants at risk Participants who received 5 mg BID for the first 2 weeks and 10 mg BID for the second 2 weeks (i.e., Week 3 and 4). At Week 5, the dosage escalated to 15 mg BID if there were no concerns in safety. For the subsequent visits, the dosage may have changed to either 10 mg BID or 15 mg BID depending on safety findings.
Infections and infestations Cellulitis	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Infections and infestations Pneumonia	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Psychiatric disorders Dissociative disorder	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Nervous system disorders Transient ischaemic attack	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Cardiac disorders Acute myocardial infarction	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Cardiac disorders Atrial fibrillation	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Cardiac disorders Myocardial ischaemia	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Gastrointestinal disorders Constipation	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Reproductive system and breast disorders Uterine fibrosis	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Injury, poisoning and procedural complications Laceration	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Surgical and medical procedures Large intestinal polypectomy	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Surgical and medical procedures Nasal polypectomy	0.00% 0/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.00% 0/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	0.42% 1/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.

Other adverse events

Other adverse events
Measure	Placebo n=303 participants at risk Participants who received placebo for 14 weeks.	DS-5565 15 mg/Day n=152 participants at risk Participants received oral administrations of DS-5565 15 mg/day with a 2 week titration (5 mg/day during 1st week and 10 mg/day during 2nd week) followed by 12 weeks fixed dose (15 mg/day).	DS-5565 20 mg/Day n=153 participants at risk Participants received oral administrations of DS-5565 20 mg/day with a 1 week titration (5 mg BID) followed by 13 weeks fixed dose (10 mg BID).	DS-5565 30 mg/Day n=155 participants at risk Participants received oral administrations of DS-5565 30 mg/day with a 2 week titration (5 mg BID during 1st week and 10 mg BID during 2nd week) followed by 12 weeks fixed dose (15 mg BID).	DS-5565 Open-label Extension n=237 participants at risk Participants who received 5 mg BID for the first 2 weeks and 10 mg BID for the second 2 weeks (i.e., Week 3 and 4). At Week 5, the dosage escalated to 15 mg BID if there were no concerns in safety. For the subsequent visits, the dosage may have changed to either 10 mg BID or 15 mg BID depending on safety findings.
Infections and infestations Nasopharyngitis	8.6% 26/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	8.6% 13/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	10.5% 16/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	12.9% 20/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	16.5% 39/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Nervous system disorders Somnolence	3.6% 11/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	13.2% 20/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	17.0% 26/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	23.9% 37/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	15.2% 36/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Nervous system disorders Dizziness	3.3% 10/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	6.6% 10/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	9.8% 15/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	15.5% 24/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	11.0% 26/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
General disorders Oedema	0.66% 2/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	1.3% 2/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	3.9% 6/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	7.1% 11/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	5.9% 14/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.
Investigations Weight increased	0.33% 1/303 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	4.6% 7/152 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	5.2% 8/153 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	5.2% 8/155 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.	9.3% 22/237 • Adverse events (AEs) were collected from after the participant signed the informed consent form and up to 7 days after the last dose of the study drug (the post-treatment follow-up visit [Visit 11]), up to 2 years 5 months. Treatment-emergent AEs were defined as any AEs that appeared after the first administration of study treatment or that worsened relative to the pre-treatment state. Safety data were reported from participants in the Safety Analysis Set who had available safety data; 2 participants in the DS-5565 open-label extension data did not have available safety data and were not included in the analysis.

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place