Trial Outcomes & Findings for Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line Treatment for Patients With Advanced Melanoma (NCT NCT02599402)

Last Updated: 2021-06-15

Results Overview

Incidence of participants with high-grade (CTCAE v4.0 grade 3-5) treatment-related, select adverse events of potentially immune-mediated etiology including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

533 participants

Primary outcome timeframe

From first dose to 30 days after last dose (up to approximately 37 months)

Results posted on

2021-06-15

Participant Flow

533 participants treated

Participant milestones

Participant milestones
Measure	Nivolumab + Ipilimumab Total Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240 mg) IV Q2W up to 21 months
Overall Study STARTED	533
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	533

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab + Ipilimumab Total Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240 mg) IV Q2W up to 21 months
Overall Study Disease progression	153
Overall Study Study drug toxicity	201
Overall Study Death	26
Overall Study Adverse Event unrelated to study drug	23
Overall Study Participant request to discontinue study treatment	13
Overall Study Participant withdrew consent	5
Overall Study Lost to Follow-up	1
Overall Study Maximum Clinical Benefit	7
Overall Study Poor/non-compliance	1
Overall Study Pregnancy	1
Overall Study Participant no longer met study criteria	7
Overall Study Other Reasons	95

Baseline Characteristics

Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line Treatment for Patients With Advanced Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240 mg) IV Q2W up to 21 months
Age, Continuous	59.0 Years STANDARD_DEVIATION 13.55 • n=93 Participants
Sex: Female, Male Female	217 Participants n=93 Participants
Sex: Female, Male Male	316 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	515 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	521 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=93 Participants

PRIMARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Hypersensitivity/Infusion Reaction: Grade 3-4	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Pulmonary: Grade 3-4	7 Participants	7 Participants	0 Participants	0 Participants	0 Participants	1 Participants	6 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Pulmonary: Grade 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Gastrointestinal: Grade 3-4	83 Participants	79 Participants	4 Participants	5 Participants	5 Participants	9 Participants	57 Participants	1 Participants	11 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Gastrointestinal: Grade 5	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Skin: Grade 3-4	35 Participants	31 Participants	4 Participants	1 Participants	3 Participants	7 Participants	20 Participants	1 Participants	4 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Skin: Grade 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Renal: Grade 3-4	10 Participants	9 Participants	1 Participants	1 Participants	0 Participants	1 Participants	8 Participants	0 Participants	1 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Renal: Grade 5	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Hepatic: Grade 3-4	82 Participants	75 Participants	7 Participants	6 Participants	2 Participants	17 Participants	56 Participants	1 Participants	6 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Hepatic: Grade 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Endocrine: Grade 3-4	58 Participants	58 Participants	0 Participants	5 Participants	2 Participants	6 Participants	43 Participants	1 Participants	6 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Endocrine: Grade 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events Hypersensitivity/Infusion Reaction: Grade 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

Incidence of participants with high-grade (grade 3-5) select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, infusion-related, or hypersensitivity

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Pulmonary: Grade 3-4	8 Participants	8 Participants	0 Participants	0 Participants	0 Participants	1 Participants	7 Participants	0 Participants	0 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Gastrointestinal: Grade 3-4	87 Participants	83 Participants	4 Participants	5 Participants	5 Participants	9 Participants	61 Participants	1 Participants	11 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Skin: Grade 3-4	39 Participants	35 Participants	4 Participants	1 Participants	3 Participants	8 Participants	22 Participants	1 Participants	5 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Renal: Grade 3-4	13 Participants	12 Participants	1 Participants	1 Participants	0 Participants	1 Participants	10 Participants	1 Participants	1 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Renal: Grade 5	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Hepatic: Grade 5	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Hypersensitivity/Infusion Reaction: Grade 3-4	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Gastrointestinal: Grade 5	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events Hepatic: Grade 3-4	101 Participants	93 Participants	8 Participants	11 Participants	4 Participants	21 Participants	67 Participants	1 Participants	8 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups with at least one select adverse event from the category

Median time to onset (grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Median Time to Onset (Grades 3-4) of Select Adverse Events Pulmonary	51.5 Days Interval 12.0 to 783.0	51.5 Days Interval 12.0 to 783.0	—	—	—	51.0 Days Interval 51.0 to 51.0	52.0 Days Interval 12.0 to 783.0	—	—
Median Time to Onset (Grades 3-4) of Select Adverse Events Gastrointestinal	49.0 Days Interval 7.0 to 582.0	49.0 Days Interval 7.0 to 582.0	61.0 Days Interval 8.0 to 91.0	83.0 Days Interval 35.0 to 543.0	42.5 Days Interval 27.0 to 543.0	39.0 Days Interval 20.0 to 95.0	49.0 Days Interval 7.0 to 582.0	7.0 Days Interval 7.0 to 7.0	79.0 Days Interval 8.0 to 281.0
Median Time to Onset (Grades 3-4) of Select Adverse Events Skin	32.0 Days Interval 4.0 to 670.0	35.0 Days Interval 4.0 to 404.0	17.5 Days Interval 7.0 to 670.0	14.0 Days Interval 14.0 to 14.0	48.0 Days Interval 8.0 to 69.0	36.5 Days Interval 14.0 to 127.0	17.5 Days Interval 4.0 to 670.0	89.0 Days Interval 89.0 to 89.0	100.0 Days Interval 10.0 to 338.0
Median Time to Onset (Grades 3-4) of Select Adverse Events Renal	52.5 Days Interval 6.0 to 540.0	43.0 Days Interval 6.0 to 223.0	540.0 Days Interval 540.0 to 540.0	106.0 Days Interval 106.0 to 106.0	—	23.0 Days Interval 23.0 to 23.0	106.0 Days Interval 14.0 to 540.0	16.0 Days Interval 16.0 to 16.0	6.0 Days Interval 6.0 to 6.0
Median Time to Onset (Grades 3-4) of Select Adverse Events Hepatic	63.0 Days Interval 5.0 to 724.0	63.0 Days Interval 5.0 to 724.0	63.0 Days Interval 13.0 to 83.0	64.0 Days Interval 41.0 to 724.0	139.0 Days Interval 22.0 to 475.0	64.0 Days Interval 16.0 to 111.0	62.0 Days Interval 5.0 to 588.0	101.0 Days Interval 101.0 to 101.0	80.0 Days Interval 8.0 to 724.0
Median Time to Onset (Grades 3-4) of Select Adverse Events Endocrine	75.0 Days Interval 7.0 to 369.0	75.0 Days Interval 7.0 to 369.0	—	67.0 Days Interval 25.0 to 130.0	153.0 Days Interval 102.0 to 204.0	70.0 Days Interval 26.0 to 98.0	71.5 Days Interval 7.0 to 369.0	114.0 Days Interval 114.0 to 114.0	39.5 Days Interval 16.0 to 115.0
Median Time to Onset (Grades 3-4) of Select Adverse Events Hypersensitivity/Infusion Reaction	291.5 Days Interval 22.0 to 561.0	291.5 Days Interval 22.0 to 561.0	—	—	—	—	22.0 Days Interval 22.0 to 22.0	—	561.0 Days Interval 561.0 to 561.0

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups with at least one select adverse event from the category

Median time to resolution (Grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Median Time to Resolution (Grades 3-4) of Select Adverse Events Pulmonary	19.0 Days Interval 5.0 to 64.0	19.0 Days Interval 5.0 to 64.0	—	—	—	6.0 Days Interval 6.0 to 6.0	30.0 Days Interval 5.0 to 64.0	—	—
Median Time to Resolution (Grades 3-4) of Select Adverse Events Gastrointestinal	22.0 Days Interval 2.0 to 684.0	22.0 Days Interval 2.0 to 684.0	NA Days Interval 8.0 to 437.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	107.5 Days Interval 18.0 to 666.0	25.0 Days Interval 6.0 to 437.0	14.0 Days Interval 6.0 to 183.0	23.0 Days Interval 2.0 to 684.0	5.0 Days Interval 5.0 to 5.0	12.0 Days Interval 4.0 to 214.0
Median Time to Resolution (Grades 3-4) of Select Adverse Events Skin	24.0 Days Interval 4.0 to 690.0	24.0 Days Interval 4.0 to 690.0	20.0 Days Interval 10.0 to 186.0	67.0 Days Interval 67.0 to 67.0	8.0 Days Interval 5.0 to 44.0	17.5 Days Interval 4.0 to 690.0	24.0 Days Interval 8.0 to 455.0	15.0 Days Interval 15.0 to 15.0	28.0 Days Interval 4.0 to 287.0
Median Time to Resolution (Grades 3-4) of Select Adverse Events Renal	19.0 Days Interval 3.0 to 66.0	23.0 Days Interval 3.0 to 66.0	11.0 Days Interval 11.0 to 11.0	7.0 Days Interval 7.0 to 7.0	—	23.0 Days Interval 23.0 to 23.0	11.0 Days Interval 3.0 to 60.0	NA Days Interval 20.0 to 20.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	66.0 Days Interval 66.0 to 66.0
Median Time to Resolution (Grades 3-4) of Select Adverse Events Hepatic	42.0 Days Interval 1.0 to 889.0	38.0 Days Interval 1.0 to 889.0	67.0 Days Interval 3.0 to 225.0	17.5 Days Interval 2.0 to 285.0	126.0 Days Interval 1.0 to 625.0	55.0 Days Interval 1.0 to 612.0	30.0 Days Interval 2.0 to 889.0	29.0 Days Interval 29.0 to 29.0	117.0 Days Interval 15.0 to 285.0
Median Time to Resolution (Grades 3-4) of Select Adverse Events Endocrine	NA Days Interval 2.0 to 1223.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 3.0 to 1019.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	—	NA Days Interval 4.0 to 950.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 5.0 to 931.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 3.0 to 670.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 4.0 to 1019.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 514.0 to 514.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 4.0 to 627.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.
Median Time to Resolution (Grades 3-4) of Select Adverse Events Hypersensitivity/Infusion Reaction	4.5 Days Interval 2.0 to 7.0	4.5 Days Interval 2.0 to 7.0	—	—	—	—	2.0 Days Interval 2.0 to 2.0	—	7.0 Days Interval 7.0 to 7.0

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups with at least one select adverse event from the category

Resolution of an adverse event (AE) is defined as a participant experiencing complete resolution or improvement to the baseline of any grade AE including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Time to Resolution of an Adverse Event (AE) Pulmonary	35.0 Days Interval 6.0 to 738.0	43.0 Days Interval 6.0 to 738.0	7.5 Days Interval 7.0 to 8.0	NA Days Interval 55.0 to 302.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 7.0 to 371.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	19.0 Days Interval 6.0 to 62.0	43.0 Days Interval 7.0 to 738.0	—	NA Days Interval 24.0 to 302.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.
Time to Resolution of an Adverse Event (AE) Renal	56.0 Days Interval 2.0 to 904.0	56.0 Days Interval 2.0 to 904.0	11.0 Days Interval 11.0 to 11.0	5.5 Days Interval 2.0 to 100.0	9.5 Days Interval 4.0 to 15.0	27.5 Days Interval 23.0 to 32.0	56.0 Days Interval 2.0 to 904.0	NA Days Interval 20.0 to 20.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 66.0 to 603.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.
Time to Resolution of an Adverse Event (AE) Hepatic	44.0 Days Interval 1.0 to 1008.0	43.0 Days Interval 1.0 to 1008.0	80.5 Days Interval 3.0 to 225.0	20.5 Days Interval 3.0 to 1008.0	97.0 Days Interval 1.0 to 650.0	34.0 Days Interval 1.0 to 612.0	37.0 Days Interval 3.0 to 912.0	129.0 Days Interval 31.0 to 129.0	29.0 Days Interval 8.0 to 1008.0
Time to Resolution of an Adverse Event (AE) Hypersensitivity/Infusion Reaction	1.0 Days Interval 1.0 to 7.0	1.0 Days Interval 1.0 to 7.0	1.0 Days Interval 1.0 to 1.0	—	—	—	1.0 Days Interval 1.0 to 7.0	—	1.0 Days Interval 1.0 to 7.0
Time to Resolution of an Adverse Event (AE) Gastrointestinal	18.0 Days Interval 1.0 to 1016.0	18.0 Days Interval 1.0 to 1016.0	12.0 Days Interval 1.0 to 468.0	36.0 Days Interval 1.0 to 720.0	14.0 Days Interval 1.0 to 527.0	14.0 Days Interval 1.0 to 183.0	19.0 Days Interval 1.0 to 1016.0	5.0 Days Interval 1.0 to 22.0	36.0 Days Interval 2.0 to 645.0
Time to Resolution of an Adverse Event (AE) Skin	89.0 Days Interval 1.0 to 1175.0	88.0 Days Interval 1.0 to 1175.0	NA Days Interval 5.0 to 1002.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	257.0 Days Interval 1.0 to 1011.0	84.0 Days Interval 5.0 to 1055.0	33.5 Days Interval 4.0 to 775.0	102.0 Days Interval 1.0 to 1175.0	46.0 Days Interval 15.0 to 625.0	59.5 Days Interval 2.0 to 952.0
Time to Resolution of an Adverse Event (AE) Endocrine	NA Days Interval 2.0 to 1223.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 2.0 to 1223.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 76.0 to 917.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 4.0 to 950.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 5.0 to 1139.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 2.0 to 759.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 4.0 to 1223.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 40.0 to 938.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Days Interval 6.0 to 1060.0 KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.

SECONDARY outcome

Timeframe: Up to approximately 37 months

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

Overall survival is defined from the time of first dosing date to the date of death. A participant who has not died will be censored at the last known date alive

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Overall Survival (OS)	NA Months Interval 33.91 to KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	NA Months Interval 34.76 to KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	11.01 Months Interval 7.23 to Insufficient data due to insufficient participant follow up.	NA Months KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	12.55 Months Interval 3.78 to 33.91	15.21 Months Interval 10.41 to 21.42	NA Months KM methodology requires having more than 50% of events to estimate the median and/or upper/lower limits.	20.83 Months Interval 1.15 to Insufficient data due to insufficient participant follow up.	34.76 Months Interval 16.69 to Insufficient data due to insufficient participant follow up.

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

The assessment of safety is measured by the incidence of participants who experienced any grade of adverse events (AEs), treatment-related AEs, serious adverse events (SAEs), and deaths

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Incidence of Participants With Adverse Events Treatment-Related AEs	484 Participants	444 Participants	40 Participants	33 Participants	26 Participants	61 Participants	332 Participants	8 Participants	35 Participants
Incidence of Participants With Adverse Events Serious Adverse Events (SAEs)	356 Participants	324 Participants	31 Participants	31 Participants	26 Participants	40 Participants	238 Participants	9 Participants	43 Participants
Incidence of Participants With Adverse Events Deaths	199 Participants	169 Participants	29 Participants	13 Participants	20 Participants	41 Participants	107 Participants	6 Participants	25 Participants
Incidence of Participants With Adverse Events Adverse Events (AEs)	533 Participants	477 Participants	55 Participants	42 Participants	32 Participants	64 Participants	365 Participants	10 Participants	62 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

The assessment of safety is measured by the incidence of participants who experienced any grade of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Incidence of Participants With Select Adverse Events Hypersensitivity/Infusion Reaction	8 Participants	7 Participants	1 Participants	0 Participants	0 Participants	0 Participants	5 Participants	0 Participants	3 Participants
Incidence of Participants With Select Adverse Events Pulmonary	28 Participants	26 Participants	2 Participants	2 Participants	2 Participants	3 Participants	21 Participants	0 Participants	2 Participants
Incidence of Participants With Select Adverse Events Gastrointestinal	252 Participants	236 Participants	16 Participants	14 Participants	13 Participants	31 Participants	175 Participants	6 Participants	27 Participants
Incidence of Participants With Select Adverse Events Renal	43 Participants	42 Participants	1 Participants	4 Participants	2 Participants	2 Participants	34 Participants	1 Participants	4 Participants
Incidence of Participants With Select Adverse Events Hepatic	185 Participants	173 Participants	12 Participants	16 Participants	7 Participants	35 Participants	128 Participants	2 Participants	13 Participants
Incidence of Participants With Select Adverse Events Endocrine	242 Participants	231 Participants	11 Participants	20 Participants	15 Participants	29 Participants	166 Participants	5 Participants	27 Participants
Incidence of Participants With Select Adverse Events Skin	319 Participants	296 Participants	23 Participants	23 Participants	17 Participants	34 Participants	228 Participants	8 Participants	32 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups with at least one on-treatment measurement of the corresponding laboratory parameter

Safety assessment is measured by the incidence of participants who experienced a liver laboratory abnormality in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Upper Limit of Normal (ULN)

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Incidence of Participants With Laboratory Abnormalities - Liver TOTAL BILIRUBIN > 2XULN	12 Participants	12 Participants	0 Participants	1 Participants	0 Participants	3 Participants	8 Participants	0 Participants	1 Participants
Incidence of Participants With Laboratory Abnormalities - Liver CONCURRENT ALT OR AST ELEVATION > 3XULN; TOTAL BILIRUBIN > 2XULN IN 30 DAYS	4 Participants	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants
Incidence of Participants With Laboratory Abnormalities - Liver ALT OR AST > 3XULN	113 Participants	106 Participants	7 Participants	11 Participants	7 Participants	21 Participants	72 Participants	2 Participants	11 Participants
Incidence of Participants With Laboratory Abnormalities - Liver ALT OR AST > 5XULN	75 Participants	69 Participants	6 Participants	4 Participants	5 Participants	13 Participants	48 Participants	1 Participants	8 Participants
Incidence of Participants With Laboratory Abnormalities - Liver ALT OR AST > 10XULN	30 Participants	27 Participants	3 Participants	0 Participants	2 Participants	4 Participants	22 Participants	0 Participants	2 Participants
Incidence of Participants With Laboratory Abnormalities - Liver ALT OR AST > 20XULN	12 Participants	11 Participants	1 Participants	0 Participants	1 Participants	2 Participants	7 Participants	0 Participants	2 Participants
Incidence of Participants With Laboratory Abnormalities - Liver CONCURRENT ALT OR AST ELEVATION > 3XULN; TOTAL BILIRUBIN > 2XULN IN 1 DAY	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose (up to approximately 37 months)

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups with at least one on-treatment TSH measurement

Safety assessment is measured by the incidence of participants who experienced a thyroid laboratory abnormality in Free T3 (FT3), Free T4 (FT4), Lower Limit of Normal (LLN)

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=449 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=410 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=39 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=35 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=26 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=49 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=313 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=51 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH > ULN	130 Participants	123 Participants	7 Participants	12 Participants	8 Participants	12 Participants	91 Participants	4 Participants	15 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH > ULN WITH TSH <= ULN AT BASELINE	113 Participants	108 Participants	5 Participants	11 Participants	6 Participants	10 Participants	79 Participants	3 Participants	15 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN	80 Participants	76 Participants	4 Participants	8 Participants	5 Participants	6 Participants	55 Participants	2 Participants	12 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN	37 Participants	35 Participants	2 Participants	3 Participants	1 Participants	4 Participants	27 Participants	2 Participants	3 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH > ULN WITH FT3/FT4 TEST MISSING	26 Participants	25 Participants	1 Participants	2 Participants	2 Participants	2 Participants	21 Participants	0 Participants	1 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH < LLN	178 Participants	169 Participants	9 Participants	14 Participants	11 Participants	23 Participants	124 Participants	4 Participants	16 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH <LLN WITH TSH >= LLN AT BASELINE	168 Participants	159 Participants	9 Participants	14 Participants	11 Participants	21 Participants	116 Participants	4 Participants	16 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN	101 Participants	98 Participants	3 Participants	7 Participants	8 Participants	12 Participants	72 Participants	2 Participants	7 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	59 Participants	53 Participants	6 Participants	5 Participants	3 Participants	8 Participants	40 Participants	1 Participants	7 Participants
Incidence of Participants With Laboratory Abnormalities - Thyroid TSH < LLN WITH FT3/FT4 TEST MISSING	26 Participants	25 Participants	1 Participants	2 Participants	0 Participants	4 Participants	19 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to approximately 37 months

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

Objective response rate is defined as the percentage of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of all treated participants

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Objective Response Rate (ORR)	44.5 Percentage of participants Interval 40.2 to 48.8	46.1 Percentage of participants Interval 41.6 to 50.7	30.9 Percentage of participants Interval 19.1 to 44.8	52.4 Percentage of participants Interval 36.4 to 68.0	43.8 Percentage of participants Interval 26.4 to 62.3	9.4 Percentage of participants Interval 3.5 to 19.3	51.2 Percentage of participants Interval 46.0 to 56.5	30.0 Percentage of participants Interval 6.7 to 65.2	43.5 Percentage of participants Interval 31.0 to 56.7

SECONDARY outcome

Timeframe: Up to approximately 37 months

Population: All treated participants and ECOG, Brain Metastasis, and Disease Subtype subgroups

Progression free survival per investigator assessment is defined as radiological evidence of progression, significant clinical symptomatic progression, or the need to introduce a non-study drug therapy.

Outcome measures

Outcome measures
Measure	Nivolumab + Ipilimumab Total n=533 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 Participants Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 Participants Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Progression Free Survival (PFS)	4.96 Months Interval 3.45 to 6.77	5.45 Months Interval 3.78 to 7.69	2.46 Months Interval 1.77 to 3.75	3.35 Months Interval 1.81 to Insufficient data due to insufficient participant follow up.	2.94 Months Interval 2.53 to 8.74	2.83 Months Interval 2.73 to 4.63	6.77 Months Interval 4.67 to 10.45	2.56 Months Interval 1.15 to 8.48	5.22 Months Interval 2.76 to 27.27

Adverse Events

Nivolumab + Ipilimumab Total

Serious events: 356 serious events

Other events: 503 other events

Deaths: 199 deaths

Nivolumab + Ipilimumab ECOG PS0-1

Serious events: 324 serious events

Other events: 453 other events

Deaths: 169 deaths

Nivolumab + Ipilimumab ECOG PS2

Serious events: 31 serious events

Other events: 49 other events

Deaths: 29 deaths

Nivolumab + Ipilimumab Brain Metastasis

Serious events: 31 serious events

Other events: 37 other events

Deaths: 13 deaths

Nivolumab + Ipilimumab Mucosal

Serious events: 26 serious events

Other events: 28 other events

Deaths: 20 deaths

Nivolumab + Ipilimumab Ocular/Uveal

Serious events: 40 serious events

Other events: 61 other events

Deaths: 41 deaths

Nivolumab + Ipilimumab Cutaneous

Serious events: 238 serious events

Other events: 347 other events

Deaths: 107 deaths

Nivolumab + Ipilimumab Acral

Serious events: 9 serious events

Other events: 10 other events

Deaths: 6 deaths

Nivolumab + Ipilimumab Other

Serious events: 43 serious events

Other events: 57 other events

Deaths: 25 deaths

Serious adverse events

Serious adverse events
Measure	Nivolumab + Ipilimumab Total n=533 participants at risk Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 participants at risk Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Cardiac disorders Myocardial infarction	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Myocarditis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Cardiac failure congestive	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Jaw cyst	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Cardiogenic shock	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Agranulocytosis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Anaemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Aplastic anaemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Autoimmune pancytopenia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Iron deficiency anaemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Lymphopenia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Blood and lymphatic system disorders Thrombocytopenia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Arrhythmia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Atrial fibrillation	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Atrial flutter	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Atrioventricular block	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Stress cardiomyopathy	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Cardiac disorders Supraventricular tachycardia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Ear and labyrinth disorders Vertigo	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Adrenal insufficiency	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.3% 6/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.1% 4/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Adrenocortical insufficiency acute	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Hyperthyroidism	1.5% 8/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.7% 8/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	2.2% 8/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Hypophysitis	4.3% 23/533 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 23/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	3.8% 14/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Hypopituitarism	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Immune-mediated hyperthyroidism	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Lymphocytic hypophysitis	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.3% 6/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 6/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Primary adrenal insufficiency	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Thyroiditis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Thyroiditis acute	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Eye disorders Autoimmune uveitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Eye disorders Diplopia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Eye disorders Photopsia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Eye disorders Retinal detachment	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Abdominal pain	0.94% 5/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.0% 5/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Abdominal pain upper	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Ascites	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Autoimmune colitis	2.3% 12/533 • From first dose to 30 days after last dose (up to approximately 37 months)	2.3% 11/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 6/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Chronic gastritis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Colitis	8.1% 43/533 • From first dose to 30 days after last dose (up to approximately 37 months)	8.6% 41/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	8.8% 32/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	9.7% 6/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Colitis ulcerative	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Constipation	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Diarrhoea	6.8% 36/533 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 34/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	7.9% 29/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Dry mouth	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Enteritis	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Enterocolitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Gastritis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Gastrointestinal toxicity	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Immune-mediated enterocolitis	1.7% 9/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.9% 9/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	2.2% 8/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Inguinal hernia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Intestinal obstruction	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Intestinal perforation	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Mouth haemorrhage	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Nausea	0.94% 5/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.0% 5/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Pancreatic failure	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Pancreatitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Pancreatitis acute	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Rectal haemorrhage	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Small intestinal obstruction	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Vomiting	0.94% 5/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Asthenia	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Chest pain	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Fatigue	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders General physical health deterioration	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Hyperthermia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Non-cardiac chest pain	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Polyserositis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Pyrexia	2.6% 14/533 • From first dose to 30 days after last dose (up to approximately 37 months)	2.9% 14/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	2.7% 10/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Autoimmune hepatitis	2.8% 15/533 • From first dose to 30 days after last dose (up to approximately 37 months)	2.9% 14/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	3.3% 12/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Cholangitis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Cholestasis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Drug-induced liver injury	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Hepatic failure	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Hepatitis	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Hepatitis acute	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Hepatobiliary disease	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Hepatocellular injury	1.5% 8/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.5% 7/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Hepatotoxicity	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Hepatobiliary disorders Immune-mediated hepatitis	2.8% 15/533 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 15/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	4.7% 3/64 • From first dose to 30 days after last dose (up to approximately 37 months)	2.5% 9/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Immune system disorders Anaphylactic shock	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Immune system disorders Cytokine release syndrome	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Immune system disorders Drug hypersensitivity	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Immune system disorders Haemophagocytic lymphohistiocytosis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Abscess limb	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Alveolar osteitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Bronchitis	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Bronchitis viral	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Campylobacter gastroenteritis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Cellulitis	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.1% 4/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Clostridium difficile infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Device related infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Encephalitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Endocarditis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Enteritis infectious	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Enterocolitis infectious	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Erysipelas	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Gastroenteritis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Gastrointestinal viral infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Herpes zoster	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Infection	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Influenza	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Lower respiratory tract infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Meningitis aseptic	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Pharyngitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Pneumococcal infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Pneumocystis jirovecii pneumonia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Pneumonia	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Post procedural cellulitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Pyoderma	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Respiratory tract infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Respiratory tract infection viral	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Rhinovirus infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Sepsis	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.0% 5/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.4% 5/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Septic arthritis streptococcal	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Septic shock	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Sinusitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Staphylococcal bacteraemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Staphylococcal sepsis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Upper respiratory tract infection	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Urinary tract infection	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Urosepsis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Viral infection	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Wound infection	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Wound infection staphylococcal	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Injury, poisoning and procedural complications Accidental overdose	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Injury, poisoning and procedural complications Clavicle fracture	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Injury, poisoning and procedural complications Infusion related reaction	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Injury, poisoning and procedural complications Overdose	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Injury, poisoning and procedural complications Post procedural fever	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Injury, poisoning and procedural complications Subdural haematoma	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Alanine aminotransferase increased	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.3% 6/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Aspartate aminotransferase increased	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations C-reactive protein increased	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations General physical condition abnormal	0.94% 5/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Liver function test increased	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Oxygen saturation decreased	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Transaminases increased	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.1% 4/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations White blood cells urine positive	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Dehydration	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Diabetes mellitus	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.3% 6/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.4% 5/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Diabetic ketoacidosis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Electrolyte imbalance	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Hypercalcaemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Hyperglycaemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Hyperkalaemia	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Hypokalaemia	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Hyponatraemia	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Ketoacidosis	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Malnutrition	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Arthritis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Back pain	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Bursitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Pain in extremity	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Pathological fracture	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Rheumatic disorder	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Spinal pain	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	13.3% 71/533 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 57/477 • From first dose to 30 days after last dose (up to approximately 37 months)	25.5% 14/55 • From first dose to 30 days after last dose (up to approximately 37 months)	31.0% 13/42 • From first dose to 30 days after last dose (up to approximately 37 months)	25.0% 8/32 • From first dose to 30 days after last dose (up to approximately 37 months)	14.1% 9/64 • From first dose to 30 days after last dose (up to approximately 37 months)	11.5% 42/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	16.1% 10/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Ataxia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Autoimmune neuropathy	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Autonomic neuropathy	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Carpal tunnel syndrome	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Cerebral haemorrhage	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Cerebrospinal fluid leakage	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Cerebrovascular accident	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	3.2% 2/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Cubital tunnel syndrome	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Dizziness	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Facial paralysis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Guillain-Barre syndrome	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Headache	1.5% 8/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.5% 7/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.9% 7/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Intercostal neuralgia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Peripheral sensory neuropathy	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Petit mal epilepsy	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Seizure	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Spinal cord compression	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Syncope	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Psychiatric disorders Anxiety	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Psychiatric disorders Confusional state	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Psychiatric disorders Psychotic disorder	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Acute kidney injury	1.9% 10/533 • From first dose to 30 days after last dose (up to approximately 37 months)	2.1% 10/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.9% 7/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Haematuria	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Immune-mediated renal disorder	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Nephritis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Renal failure	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Tubulointerstitial nephritis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Renal and urinary disorders Urinary tract obstruction	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Reproductive system and breast disorders Metrorrhagia	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.0% 5/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 6/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 6/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.3% 6/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.1% 4/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pleurisy	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 9/533 • From first dose to 30 days after last dose (up to approximately 37 months)	1.9% 9/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	1.9% 7/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.56% 3/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.63% 3/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pulmonary haematoma	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Dermatitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Dermatitis allergic	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Drug eruption	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Erythema	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Lichen planus	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Pemphigoid	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Psoriasis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Rash	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.55% 2/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.75% 4/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.84% 4/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.82% 3/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Deep vein thrombosis	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Hypertension	0.38% 2/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.42% 2/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Hypotension	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Peripheral arterial occlusive disease	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Shock	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Vasculitis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Vein collapse	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.21% 1/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.27% 1/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Venous thrombosis	0.19% 1/533 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/32 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/64 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)

Other adverse events

Other adverse events
Measure	Nivolumab + Ipilimumab Total n=533 participants at risk Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months	Nivolumab + Ipilimumab ECOG PS0-1 n=477 participants at risk Part 1: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 subgroup	Nivolumab + Ipilimumab ECOG PS2 n=55 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 subgroup	Nivolumab + Ipilimumab Brain Metastasis n=42 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Brain Metastasis subgroup	Nivolumab + Ipilimumab Mucosal n=32 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Mucosal	Nivolumab + Ipilimumab Ocular/Uveal n=64 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Ocular/Uveal	Nivolumab + Ipilimumab Cutaneous n=365 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Cutaneous	Nivolumab + Ipilimumab Acral n=10 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Acral	Nivolumab + Ipilimumab Other n=62 participants at risk Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV Q3W x 4 doses up to 3 months Then Part 2: Nivolumab (3mg/kg or 240mg) IV Q2W up to 21 months Participants were grouped in to Disease Subtype subgroup Other
Blood and lymphatic system disorders Anaemia	10.7% 57/533 • From first dose to 30 days after last dose (up to approximately 37 months)	10.5% 50/477 • From first dose to 30 days after last dose (up to approximately 37 months)	12.7% 7/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 2/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	9.6% 35/365 • From first dose to 30 days after last dose (up to approximately 37 months)	30.0% 3/10 • From first dose to 30 days after last dose (up to approximately 37 months)	17.7% 11/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Hyperthyroidism	18.4% 98/533 • From first dose to 30 days after last dose (up to approximately 37 months)	20.1% 96/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	16.7% 7/42 • From first dose to 30 days after last dose (up to approximately 37 months)	21.9% 7/32 • From first dose to 30 days after last dose (up to approximately 37 months)	21.9% 14/64 • From first dose to 30 days after last dose (up to approximately 37 months)	18.9% 69/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	12.9% 8/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Hypophysitis	5.6% 30/533 • From first dose to 30 days after last dose (up to approximately 37 months)	5.7% 27/477 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 3/55 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 3/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	6.8% 25/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Endocrine disorders Hypothyroidism	20.6% 110/533 • From first dose to 30 days after last dose (up to approximately 37 months)	21.8% 104/477 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 6/55 • From first dose to 30 days after last dose (up to approximately 37 months)	19.0% 8/42 • From first dose to 30 days after last dose (up to approximately 37 months)	28.1% 9/32 • From first dose to 30 days after last dose (up to approximately 37 months)	15.6% 10/64 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 73/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	25.8% 16/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Abdominal pain	13.7% 73/533 • From first dose to 30 days after last dose (up to approximately 37 months)	14.9% 71/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 8/64 • From first dose to 30 days after last dose (up to approximately 37 months)	14.2% 52/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	12.9% 8/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Abdominal pain upper	6.8% 36/533 • From first dose to 30 days after last dose (up to approximately 37 months)	6.9% 33/477 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 3/55 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 3/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 8/64 • From first dose to 30 days after last dose (up to approximately 37 months)	6.0% 22/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Constipation	15.6% 83/533 • From first dose to 30 days after last dose (up to approximately 37 months)	16.1% 77/477 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 6/55 • From first dose to 30 days after last dose (up to approximately 37 months)	28.6% 12/42 • From first dose to 30 days after last dose (up to approximately 37 months)	21.9% 7/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	16.7% 61/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	12.9% 8/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Diarrhoea	42.0% 224/533 • From first dose to 30 days after last dose (up to approximately 37 months)	43.8% 209/477 • From first dose to 30 days after last dose (up to approximately 37 months)	27.3% 15/55 • From first dose to 30 days after last dose (up to approximately 37 months)	31.0% 13/42 • From first dose to 30 days after last dose (up to approximately 37 months)	40.6% 13/32 • From first dose to 30 days after last dose (up to approximately 37 months)	42.2% 27/64 • From first dose to 30 days after last dose (up to approximately 37 months)	42.2% 154/365 • From first dose to 30 days after last dose (up to approximately 37 months)	50.0% 5/10 • From first dose to 30 days after last dose (up to approximately 37 months)	40.3% 25/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Dry mouth	9.6% 51/533 • From first dose to 30 days after last dose (up to approximately 37 months)	10.5% 50/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 2/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	10.1% 37/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	9.7% 6/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Nausea	29.3% 156/533 • From first dose to 30 days after last dose (up to approximately 37 months)	30.2% 144/477 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 11/55 • From first dose to 30 days after last dose (up to approximately 37 months)	23.8% 10/42 • From first dose to 30 days after last dose (up to approximately 37 months)	25.0% 8/32 • From first dose to 30 days after last dose (up to approximately 37 months)	37.5% 24/64 • From first dose to 30 days after last dose (up to approximately 37 months)	28.8% 105/365 • From first dose to 30 days after last dose (up to approximately 37 months)	50.0% 5/10 • From first dose to 30 days after last dose (up to approximately 37 months)	22.6% 14/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Gastrointestinal disorders Vomiting	15.4% 82/533 • From first dose to 30 days after last dose (up to approximately 37 months)	15.7% 75/477 • From first dose to 30 days after last dose (up to approximately 37 months)	12.7% 7/55 • From first dose to 30 days after last dose (up to approximately 37 months)	21.4% 9/42 • From first dose to 30 days after last dose (up to approximately 37 months)	15.6% 5/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	16.4% 60/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	14.5% 9/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Asthenia	18.0% 96/533 • From first dose to 30 days after last dose (up to approximately 37 months)	17.2% 82/477 • From first dose to 30 days after last dose (up to approximately 37 months)	25.5% 14/55 • From first dose to 30 days after last dose (up to approximately 37 months)	19.0% 8/42 • From first dose to 30 days after last dose (up to approximately 37 months)	15.6% 5/32 • From first dose to 30 days after last dose (up to approximately 37 months)	17.2% 11/64 • From first dose to 30 days after last dose (up to approximately 37 months)	17.3% 63/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	24.2% 15/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Chills	5.1% 27/533 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 26/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	4.9% 18/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Fatigue	33.4% 178/533 • From first dose to 30 days after last dose (up to approximately 37 months)	36.3% 173/477 • From first dose to 30 days after last dose (up to approximately 37 months)	9.1% 5/55 • From first dose to 30 days after last dose (up to approximately 37 months)	28.6% 12/42 • From first dose to 30 days after last dose (up to approximately 37 months)	28.1% 9/32 • From first dose to 30 days after last dose (up to approximately 37 months)	28.1% 18/64 • From first dose to 30 days after last dose (up to approximately 37 months)	35.3% 129/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	33.9% 21/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Influenza like illness	7.7% 41/533 • From first dose to 30 days after last dose (up to approximately 37 months)	8.6% 41/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	4.7% 3/64 • From first dose to 30 days after last dose (up to approximately 37 months)	8.5% 31/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Oedema peripheral	6.4% 34/533 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 31/477 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 3/55 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 3/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	4.9% 18/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	8.1% 5/62 • From first dose to 30 days after last dose (up to approximately 37 months)
General disorders Pyrexia	24.4% 130/533 • From first dose to 30 days after last dose (up to approximately 37 months)	23.3% 111/477 • From first dose to 30 days after last dose (up to approximately 37 months)	34.5% 19/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	21.9% 7/32 • From first dose to 30 days after last dose (up to approximately 37 months)	20.3% 13/64 • From first dose to 30 days after last dose (up to approximately 37 months)	24.9% 91/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	27.4% 17/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Infections and infestations Nasopharyngitis	9.4% 50/533 • From first dose to 30 days after last dose (up to approximately 37 months)	10.3% 49/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	14.3% 6/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	7.9% 29/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	16.1% 10/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Alanine aminotransferase increased	18.9% 101/533 • From first dose to 30 days after last dose (up to approximately 37 months)	19.1% 91/477 • From first dose to 30 days after last dose (up to approximately 37 months)	18.2% 10/55 • From first dose to 30 days after last dose (up to approximately 37 months)	21.4% 9/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	31.2% 20/64 • From first dose to 30 days after last dose (up to approximately 37 months)	18.9% 69/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	11.3% 7/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Amylase increased	7.3% 39/533 • From first dose to 30 days after last dose (up to approximately 37 months)	7.3% 35/477 • From first dose to 30 days after last dose (up to approximately 37 months)	7.3% 4/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	7.9% 29/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 4/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Aspartate aminotransferase increased	15.9% 85/533 • From first dose to 30 days after last dose (up to approximately 37 months)	16.1% 77/477 • From first dose to 30 days after last dose (up to approximately 37 months)	14.5% 8/55 • From first dose to 30 days after last dose (up to approximately 37 months)	19.0% 8/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	25.0% 16/64 • From first dose to 30 days after last dose (up to approximately 37 months)	16.2% 59/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	8.1% 5/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Blood alkaline phosphatase increased	5.3% 28/533 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 26/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 3/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	4.9% 18/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Gamma-glutamyltransferase increased	5.3% 28/533 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 26/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	6.6% 24/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Lipase increased	14.1% 75/533 • From first dose to 30 days after last dose (up to approximately 37 months)	14.3% 68/477 • From first dose to 30 days after last dose (up to approximately 37 months)	12.7% 7/55 • From first dose to 30 days after last dose (up to approximately 37 months)	23.8% 10/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	15.6% 57/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	12.9% 8/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Investigations Weight decreased	9.9% 53/533 • From first dose to 30 days after last dose (up to approximately 37 months)	10.3% 49/477 • From first dose to 30 days after last dose (up to approximately 37 months)	7.3% 4/55 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 3/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 4/64 • From first dose to 30 days after last dose (up to approximately 37 months)	11.2% 41/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Decreased appetite	21.6% 115/533 • From first dose to 30 days after last dose (up to approximately 37 months)	22.6% 108/477 • From first dose to 30 days after last dose (up to approximately 37 months)	12.7% 7/55 • From first dose to 30 days after last dose (up to approximately 37 months)	28.6% 12/42 • From first dose to 30 days after last dose (up to approximately 37 months)	21.9% 7/32 • From first dose to 30 days after last dose (up to approximately 37 months)	15.6% 10/64 • From first dose to 30 days after last dose (up to approximately 37 months)	23.3% 85/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	19.4% 12/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Metabolism and nutrition disorders Hypokalaemia	7.5% 40/533 • From first dose to 30 days after last dose (up to approximately 37 months)	7.5% 36/477 • From first dose to 30 days after last dose (up to approximately 37 months)	7.3% 4/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 2/32 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 7/64 • From first dose to 30 days after last dose (up to approximately 37 months)	7.4% 27/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Arthralgia	14.1% 75/533 • From first dose to 30 days after last dose (up to approximately 37 months)	15.3% 73/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 2/32 • From first dose to 30 days after last dose (up to approximately 37 months)	14.1% 9/64 • From first dose to 30 days after last dose (up to approximately 37 months)	14.2% 52/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	17.7% 11/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Back pain	9.2% 49/533 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 45/477 • From first dose to 30 days after last dose (up to approximately 37 months)	7.3% 4/55 • From first dose to 30 days after last dose (up to approximately 37 months)	14.3% 6/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	4.7% 3/64 • From first dose to 30 days after last dose (up to approximately 37 months)	11.0% 40/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 4/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.4% 29/533 • From first dose to 30 days after last dose (up to approximately 37 months)	5.9% 28/477 • From first dose to 30 days after last dose (up to approximately 37 months)	1.8% 1/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	4.7% 3/64 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 20/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Myalgia	7.5% 40/533 • From first dose to 30 days after last dose (up to approximately 37 months)	7.5% 36/477 • From first dose to 30 days after last dose (up to approximately 37 months)	7.3% 4/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 2/32 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 4/64 • From first dose to 30 days after last dose (up to approximately 37 months)	7.7% 28/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	9.7% 6/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Musculoskeletal and connective tissue disorders Pain in extremity	6.8% 36/533 • From first dose to 30 days after last dose (up to approximately 37 months)	6.9% 33/477 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 3/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	18.8% 6/32 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 4/64 • From first dose to 30 days after last dose (up to approximately 37 months)	5.2% 19/365 • From first dose to 30 days after last dose (up to approximately 37 months)	30.0% 3/10 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 4/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Nervous system disorders Headache	22.0% 117/533 • From first dose to 30 days after last dose (up to approximately 37 months)	23.1% 110/477 • From first dose to 30 days after last dose (up to approximately 37 months)	12.7% 7/55 • From first dose to 30 days after last dose (up to approximately 37 months)	31.0% 13/42 • From first dose to 30 days after last dose (up to approximately 37 months)	15.6% 5/32 • From first dose to 30 days after last dose (up to approximately 37 months)	20.3% 13/64 • From first dose to 30 days after last dose (up to approximately 37 months)	23.8% 87/365 • From first dose to 30 days after last dose (up to approximately 37 months)	30.0% 3/10 • From first dose to 30 days after last dose (up to approximately 37 months)	14.5% 9/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Psychiatric disorders Insomnia	10.9% 58/533 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 52/477 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 6/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 4/64 • From first dose to 30 days after last dose (up to approximately 37 months)	12.9% 47/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 4/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Cough	20.3% 108/533 • From first dose to 30 days after last dose (up to approximately 37 months)	20.5% 98/477 • From first dose to 30 days after last dose (up to approximately 37 months)	18.2% 10/55 • From first dose to 30 days after last dose (up to approximately 37 months)	16.7% 7/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	18.8% 12/64 • From first dose to 30 days after last dose (up to approximately 37 months)	21.4% 78/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	21.0% 13/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 59/533 • From first dose to 30 days after last dose (up to approximately 37 months)	11.7% 56/477 • From first dose to 30 days after last dose (up to approximately 37 months)	5.5% 3/55 • From first dose to 30 days after last dose (up to approximately 37 months)	7.1% 3/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	11.0% 40/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	12.9% 8/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Pruritus	27.4% 146/533 • From first dose to 30 days after last dose (up to approximately 37 months)	28.3% 135/477 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 11/55 • From first dose to 30 days after last dose (up to approximately 37 months)	26.2% 11/42 • From first dose to 30 days after last dose (up to approximately 37 months)	34.4% 11/32 • From first dose to 30 days after last dose (up to approximately 37 months)	20.3% 13/64 • From first dose to 30 days after last dose (up to approximately 37 months)	27.9% 102/365 • From first dose to 30 days after last dose (up to approximately 37 months)	40.0% 4/10 • From first dose to 30 days after last dose (up to approximately 37 months)	25.8% 16/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Rash	15.4% 82/533 • From first dose to 30 days after last dose (up to approximately 37 months)	15.9% 76/477 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 6/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 7/64 • From first dose to 30 days after last dose (up to approximately 37 months)	16.2% 59/365 • From first dose to 30 days after last dose (up to approximately 37 months)	30.0% 3/10 • From first dose to 30 days after last dose (up to approximately 37 months)	14.5% 9/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Rash macular	6.2% 33/533 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 31/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 2/42 • From first dose to 30 days after last dose (up to approximately 37 months)	12.5% 4/32 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 2/64 • From first dose to 30 days after last dose (up to approximately 37 months)	6.3% 23/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	12.0% 64/533 • From first dose to 30 days after last dose (up to approximately 37 months)	12.2% 58/477 • From first dose to 30 days after last dose (up to approximately 37 months)	10.9% 6/55 • From first dose to 30 days after last dose (up to approximately 37 months)	11.9% 5/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	7.8% 5/64 • From first dose to 30 days after last dose (up to approximately 37 months)	13.4% 49/365 • From first dose to 30 days after last dose (up to approximately 37 months)	20.0% 2/10 • From first dose to 30 days after last dose (up to approximately 37 months)	8.1% 5/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Rash pruritic	6.2% 33/533 • From first dose to 30 days after last dose (up to approximately 37 months)	6.5% 31/477 • From first dose to 30 days after last dose (up to approximately 37 months)	3.6% 2/55 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/42 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 3/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	7.7% 28/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Skin and subcutaneous tissue disorders Vitiligo	12.6% 67/533 • From first dose to 30 days after last dose (up to approximately 37 months)	12.2% 58/477 • From first dose to 30 days after last dose (up to approximately 37 months)	16.4% 9/55 • From first dose to 30 days after last dose (up to approximately 37 months)	16.7% 7/42 • From first dose to 30 days after last dose (up to approximately 37 months)	6.2% 2/32 • From first dose to 30 days after last dose (up to approximately 37 months)	1.6% 1/64 • From first dose to 30 days after last dose (up to approximately 37 months)	14.8% 54/365 • From first dose to 30 days after last dose (up to approximately 37 months)	10.0% 1/10 • From first dose to 30 days after last dose (up to approximately 37 months)	14.5% 9/62 • From first dose to 30 days after last dose (up to approximately 37 months)
Vascular disorders Hypertension	5.1% 27/533 • From first dose to 30 days after last dose (up to approximately 37 months)	5.7% 27/477 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/55 • From first dose to 30 days after last dose (up to approximately 37 months)	2.4% 1/42 • From first dose to 30 days after last dose (up to approximately 37 months)	3.1% 1/32 • From first dose to 30 days after last dose (up to approximately 37 months)	9.4% 6/64 • From first dose to 30 days after last dose (up to approximately 37 months)	4.7% 17/365 • From first dose to 30 days after last dose (up to approximately 37 months)	0.00% 0/10 • From first dose to 30 days after last dose (up to approximately 37 months)	4.8% 3/62 • From first dose to 30 days after last dose (up to approximately 37 months)

Additional Information

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Bristol-Myers Squibb

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Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER