Trial Outcomes & Findings for Efficacy Study of Nivolumab Compared to Docetaxel in Subjects Previously Treated With Advanced or Metastatic Non Small Cell Lung Cancer (NCT NCT02613507)

NCT ID: NCT02613507

Last Updated: 2024-11-19

Results Overview

OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 504 participants
• Primary outcome timeframe: From randomization to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)
• Results posted on: 2024-11-19

Participant Flow

Participant milestones

Measure	Nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Pre-Treamtent STARTED	338	166
Pre-Treamtent COMPLETED	337	156
Pre-Treamtent NOT COMPLETED	1	10
Treatment STARTED	337	156
Treatment Crossover to Nivolumab	0	9
Treatment COMPLETED	0	0
Treatment NOT COMPLETED	337	156

Reasons for withdrawal

Measure	Nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Pre-Treamtent Participant request to discontinue study treatment	0	5
Pre-Treamtent Participant withdrew consent	0	4
Pre-Treamtent Participant no longer meets study criteria	1	1
Treatment Not reported	3	0
Treatment Other reasons	8	0
Treatment Participant no longer meets criteria	3	0
Treatment Maximum clinical benefit	5	10
Treatment Lost to Follow-up	1	0
Treatment Participant withdrew consent	0	2
Treatment Participant request to discontinue study treatment	13	17
Treatment Adverse event unrelated to study drug	20	3
Treatment Death	2	0
Treatment Study drug toxicity	19	14
Treatment Disease progression	263	110

Baseline Characteristics

Efficacy Study of Nivolumab Compared to Docetaxel in Subjects Previously Treated With Advanced or Metastatic Non Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity	Total n=504 Participants Total of all reporting groups
Age, Continuous	59.1 Years STANDARD_DEVIATION 9.07 • n=5 Participants	59.3 Years STANDARD_DEVIATION 8.13 • n=7 Participants	59.1 Years STANDARD_DEVIATION 8.77 • n=5 Participants
Sex/Gender, Customized Male	263 Participants n=5 Participants	134 Participants n=7 Participants	397 Participants n=5 Participants
Sex/Gender, Customized Female	75 Participants n=5 Participants	32 Participants n=7 Participants	107 Participants n=5 Participants
Race/Ethnicity, Customized White	30 Participants n=5 Participants	15 Participants n=7 Participants	45 Participants n=5 Participants
Race/Ethnicity, Customized Chinese	306 Participants n=5 Participants	151 Participants n=7 Participants	457 Participants n=5 Participants
Race/Ethnicity, Customized Asian Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)

Population: All randomized participants

OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Median Overall Survival	11.99 Months Interval 10.35 to 14.0	9.63 Months Interval 7.62 to 11.24

PRIMARY outcome

Timeframe: From first dose to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)

Population: All randomized participants

OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive. Rates provided are Kaplan-Meier estimates.

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Overall Survival Rate Rate at 6 months	72.4 percentage Interval 67.3 to 76.9	64.8 percentage Interval 56.8 to 71.6
Overall Survival Rate Rate at 12 months	49.7 percentage Interval 44.1 to 55.0	38.8 percentage Interval 31.1 to 46.5

SECONDARY outcome

Timeframe: From date of first dose up to partial or complete response (up to approximately 90 months)

Population: All randomized participants

Investigator assessed ORR was defined as the number of participants whose best objective response (BOR) was a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator, divided by the number of randomized participants.

CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Objective Response Rate (ORR) All randomized participants	17.5 Percentage of participants Interval 13.6 to 21.9	4.2 Percentage of participants Interval 1.7 to 8.5
Objective Response Rate (ORR) Squamous NSCLC	21.1 Percentage of participants Interval 14.5 to 29.0	1.5 Percentage of participants Interval 0.0 to 8.0
Objective Response Rate (ORR) Non-Squamous NSCLC	15.1 Percentage of participants Interval 10.5 to 20.8	6.1 Percentage of participants Interval 2.3 to 12.7
Objective Response Rate (ORR) PD-L1 >= 1%	17.3 Percentage of participants Interval 11.9 to 23.8	6.0 Percentage of participants Interval 2.0 to 13.3
Objective Response Rate (ORR) PD-L1 < 1%	18.1 Percentage of participants Interval 12.1 to 25.6	3.0 Percentage of participants Interval 0.4 to 10.4
Objective Response Rate (ORR) PD-L1 Non-quantifiable	15.6 Percentage of participants Interval 5.3 to 32.8	NA Percentage of participants Interval 0.0 to 21.8 NA= Number not calculated due to insufficient number of events.
Objective Response Rate (ORR) Chinese	17.2 Percentage of participants Interval 13.1 to 22.0	3.4 Percentage of participants Interval 1.1 to 7.7
Objective Response Rate (ORR) Non-Chinese	19.4 Percentage of participants Interval 8.2 to 36.0	11.8 Percentage of participants Interval 1.5 to 36.4

SECONDARY outcome

Timeframe: From randomization to the date of death or date participant was last known to be alive (up to approximately 90 months)

Population: All randomized participants

OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. Test stratified by histology (SQ vs NSQ), PD-L1 status at 1% expression level (positive vs negative/unevaluable).

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Overall Survival (OS) in Subpopulations Chinese participants	11.76 Months Interval 10.18 to 13.8	8.57 Months Interval 6.93 to 10.25
Overall Survival (OS) in Subpopulations Greater than/equal to 1% PD-L1 expression	11.99 Months Interval 10.18 to 14.55	7.89 Months Interval 5.32 to 9.63
Overall Survival (OS) in Subpopulations Less than 1% PD-L1 expression	11.37 Months Interval 8.84 to 15.34	10.25 Months Interval 7.62 to 13.83
Overall Survival (OS) in Subpopulations Non-quantifiable PD-L1 Expression	15.57 Months Interval 7.1 to 20.44	16.30 Months Interval 5.45 to 26.12
Overall Survival (OS) in Subpopulations Histologically Squamous	11.70 Months Interval 8.87 to 14.0	7.89 Months Interval 5.88 to 11.2
Overall Survival (OS) in Subpopulations Histologically Non-squamous	11.86 Months Interval 9.4 to 15.34	10.22 Months Interval 7.82 to 13.11
Overall Survival (OS) in Subpopulations Non-Chinese participants	12.98 Months Interval 8.61 to 20.57	16.30 Months Interval 5.16 to 21.36

SECONDARY outcome

Timeframe: From the time of randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 90 months)

Population: All randomized participants

PFS was defined as the time from randomization to the date of the first documented tumor progression as determined by investigators per RECIST 1.1, or death due to any cause. Clinical deterioration in the absence of unequivocal evidence of progression was not considered progression for purposes of determining PFS. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who did not have disease progression or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die were censored at the randomization date. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative RT of non-target bone lesions, skin lesions or CNS lesions) without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy.

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Progression Free Survival (PFS) All randomized participants	2.79 Months Interval 2.37 to 3.65	2.76 Months Interval 1.81 to 3.02
Progression Free Survival (PFS) Histologically Squamous	2.92 Months Interval 2.37 to 4.17	2.66 Months Interval 1.45 to 2.92
Progression Free Survival (PFS) Histologically Non-Squamous	2.60 Months Interval 1.54 to 3.91	2.83 Months Interval 1.64 to 4.11
Progression Free Survival (PFS) PD-L1 >= 1%	2.76 Months Interval 1.68 to 4.01	2.56 Months Interval 1.48 to 2.99
Progression Free Survival (PFS) PD-L1 < 1%	2.86 Months Interval 1.71 to 4.11	2.78 Months Interval 1.41 to 4.24
Progression Free Survival (PFS) PD-L1 Non-quantifiable	2.00 Months Interval 1.35 to 5.55	4.07 Months Interval 1.41 to 6.93
Progression Free Survival (PFS) Chinese participants	2.76 Months Interval 2.04 to 3.35	2.69 Months Interval 1.54 to 2.83
Progression Free Survival (PFS) Non-Chinese participants	3.50 Months Interval 1.48 to 9.4	8.48 Months Interval 2.23 to 16.3

SECONDARY outcome

Timeframe: From the time of randomization up to 6 months

Population: All randomized participants

Clinical deterioration in the absence of unequivocal evidence of progression (per RECIST 1.1) is not considered progression for purposes of determining PFS. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not have disease progression or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy. Six month progression-free survival rate as estimated using the Kaplan-Meier method

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Progression Free Survival Rate	29.3 Percentage Interval 24.4 to 34.3	24.8 Percentage Interval 18.0 to 32.1

SECONDARY outcome

Timeframe: From randomization up to disease progression, death, or last dose (up to approximately 17 months)

Population: All randomized participants with at least 8 months of follow-up at the time of TTF analysis. The clinical database cutoff date will occur when the first approximately 380 randomized participants will have at least 8-month of follow-up.

TTF was defined as the minimum of the time from randomization to disease progression (per RECIST 1.1 or clinical), death or last dose date if a participant discontinued from treatment for any reasons other than "maximum clinical benefit" and "administrative reasons by sponsor". TTF was considered as event at the randomization date for participants who were randomized but not treated. TTF was censored at the last dose date for participants who discontinued treatment due to "maximum clinical benefit" or "administrative reasons by sponsor". TTF was censored at the last dose date for participants who continued on treatment without progression or death.

This outcome measure was prespecified in the protocol to only be evaluated through the first Interim Analysis, which occurred in June 2017.

Outcome measures

Measure	Nivolumab n=258 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=131 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Time to Treatment Failure (TTF)	2.60 Months Interval 1.81 to 2.92	1.51 Months Interval 1.41 to 2.23

SECONDARY outcome

Timeframe: From first dose up to 100 days after last dose (up to 93 months)

Population: All treated participants

A treatment-related Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and is determined to be associated with the study treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

Outcome measures

Measure	Nivolumab n=337 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=156 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Number of Participants Experiencing Treatment-Related Adverse Events (AEs)	220 Participants	131 Participants

SECONDARY outcome

Timeframe: From first dose up to 100 days after last dose (up to 93 months)

Population: All treated participants

A treatment-related Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization and is determined to be associated with the study treatment.

Outcome measures

Measure	Nivolumab n=337 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=156 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Number of Participants Experiencing Treatment-Related Serious Adverse Events (SAEs)	34 Participants	25 Participants

SECONDARY outcome

Timeframe: At Week 12 and Week 24

Population: All randomized participants

Disease-Related Symptom Deterioration Rate is the percentage of participants with >=10 points increase from baseline in Average Symptom Burden Index (ASBI) score at any time between randomization and the timepoints. The Lung Cancer Symptom Scale (LCSS) measures 6 items (loss of appetite, fatigue, coughing, shortness of breath, hemoptysis, pain) and 3 symptom burden items (disease-related functional limitations, quality of life) with responses captured using a 100mm visual analog scale (VAS). Scores range from 0 (highest quality of life) to 100 (worst quality of life) and is derived by dividing the length of the line drawn from the lowest possible response to the patient's response by the length of the VAS and multiplying the result by 100. An ASBI score can be derived as the mean of scores for the 6 symptom-related items with a clinically meaningful change in ASBI score being 10 points and a meaningful deterioration in symptoms is a mean post-baseline score change >= 10 points.

Outcome measures

Measure	Nivolumab n=338 Participants 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=166 Participants 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity
Disease Related Symptom Deterioration Rate by Week 12 and Week 24 Week 12	29.9 Percentage of participants Interval 25.0 to 35.1	40.4 Percentage of participants Interval 32.8 to 48.2
Disease Related Symptom Deterioration Rate by Week 12 and Week 24 Week 24	34.6 Percentage of participants Interval 29.6 to 40.0	42.2 Percentage of participants Interval 34.6 to 50.1

Adverse Events

Nivolumab

Serious events: 183 serious events

Other events: 318 other events

Deaths: 294 deaths

Docetaxel

Serious events: 73 serious events

Other events: 146 other events

Deaths: 146 deaths

Cross-over Nivolumab

Serious events: 4 serious events

Other events: 9 other events

Deaths: 8 deaths

Serious adverse events

Measure	Nivolumab n=337 participants at risk 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=156 participants at risk 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity	Cross-over Nivolumab n=9 participants at risk Participants from the Docetaxel arm who changed treatment arms to receive Nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity
Blood and lymphatic system disorders Agranulocytosis	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Anaemia	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Febrile neutropenia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.8% 6/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Granulocytopenia	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Leukopenia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Myelosuppression	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Neutropenia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Thrombocytopenia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Acute left ventricular failure	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Arrhythmia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Atrial fibrillation	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Cardiac tamponade	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Supraventricular extrasystoles	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Ventricular extrasystoles	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Diarrhoea	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Duodenal perforation	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Dysphagia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Haematochezia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Immune-mediated enterocolitis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Inguinal hernia	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Intestinal obstruction	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Malignant ascites	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Oesophageal ulcer	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Vomiting	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Death	1.5% 5/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Disease progression	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Fatigue	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Non-cardiac chest pain	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Pain	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Pyrexia	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Sudden death	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Hepatobiliary disorders Bile duct stone	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Hepatobiliary disorders Drug-induced liver injury	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Hepatobiliary disorders Hepatic function abnormal	1.2% 4/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Immune system disorders Anaphylactic reaction	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Anal abscess	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Bacteraemia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Bronchitis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Gastroenteritis	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Herpes zoster	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Infection	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Lower respiratory tract infection	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Lung abscess	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Perinephritis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Pneumonia	11.0% 37/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.1% 8/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Pneumonia aspiration	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Sepsis	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Septic shock	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Tuberculosis	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Upper respiratory tract infection	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	2.6% 4/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Wound infection	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Injury, poisoning and procedural complications Fracture	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Injury, poisoning and procedural complications Joint injury	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Injury, poisoning and procedural complications Rib fracture	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Injury, poisoning and procedural complications Spinal compression fracture	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Injury, poisoning and procedural complications Tracheal haemorrhage	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Alanine aminotransferase increased	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Amylase increased	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Aspartate aminotransferase increased	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Body temperature increased	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Electrocardiogram QT prolonged	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Lipase increased	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Neutrophil count decreased	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	2.6% 4/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Platelet count decreased	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations White blood cell count decreased	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Decreased appetite	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypercalcaemia	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hyperglycaemia	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Back pain	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Myopathy	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Pain in extremity	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Pathological fracture	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone cancer metastatic	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	27.0% 91/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	23.1% 36/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericardial effusion malignant	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Altered state of consciousness	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Cerebral infarction	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Guillain-Barre syndrome	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Haemorrhagic stroke	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Headache	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Renal and urinary disorders Acute kidney injury	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Renal and urinary disorders Nephrolithiasis	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Renal and urinary disorders Renal impairment	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Renal and urinary disorders Urinary retention	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Atelectasis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Bronchial haemorrhage	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.2% 4/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	2.6% 4/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Emphysema	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Haemothorax	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Immune-mediated lung disease	0.89% 3/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.7% 9/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Mediastinal mass	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.89% 3/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.7% 9/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Productive cough	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.89% 3/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Skin and subcutaneous tissue disorders Erythema	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Skin and subcutaneous tissue disorders Rash	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Skin and subcutaneous tissue disorders Skin oedema	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Vascular disorders Circulatory collapse	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)

Other adverse events

Measure	Nivolumab n=337 participants at risk 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity	Docetaxel n=156 participants at risk 75 mg/m² every 3 weeks until disease progression or unacceptable toxicity	Cross-over Nivolumab n=9 participants at risk Participants from the Docetaxel arm who changed treatment arms to receive Nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity
Blood and lymphatic system disorders Anaemia	34.7% 117/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	42.3% 66/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	44.4% 4/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Leukopenia	9.2% 31/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	20.5% 32/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Myelosuppression	2.1% 7/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	7.1% 11/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Neutropenia	6.2% 21/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	19.9% 31/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Blood and lymphatic system disorders Thrombocytopenia	6.5% 22/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	6.4% 10/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Atrial fibrillation	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Cardiac disorders Palpitations	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Endocrine disorders Hypothyroidism	5.3% 18/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Abdominal distension	4.7% 16/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.8% 6/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Constipation	13.9% 47/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	10.9% 17/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	44.4% 4/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Diarrhoea	10.7% 36/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	9.0% 14/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Faeces hard	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Gastritis	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Nausea	11.3% 38/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	10.9% 17/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	33.3% 3/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Toothache	3.0% 10/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Gastrointestinal disorders Vomiting	8.0% 27/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.5% 18/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Asthenia	7.7% 26/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	8.3% 13/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Chest discomfort	4.5% 15/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.1% 8/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Chest pain	1.5% 5/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Fatigue	31.2% 105/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	39.7% 62/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Malaise	1.8% 6/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Non-cardiac chest pain	12.5% 42/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.8% 9/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Oedema peripheral	3.9% 13/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.8% 9/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Pain	10.1% 34/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	9.6% 15/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
General disorders Pyrexia	17.5% 59/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	17.9% 28/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Hepatobiliary disorders Hepatic function abnormal	5.0% 17/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.9% 3/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Immune system disorders Drug hypersensitivity	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Bronchitis	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations COVID-19	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Herpes zoster	0.89% 3/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Pneumonia	10.1% 34/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	9.0% 14/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Infections and infestations Upper respiratory tract infection	11.3% 38/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.1% 8/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Alanine aminotransferase increased	19.6% 66/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.5% 18/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Amylase increased	11.3% 38/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.9% 3/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Aspartate aminotransferase increased	18.7% 63/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	7.1% 11/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Bilirubin conjugated increased	4.2% 14/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.9% 3/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Blood albumin decreased	3.6% 12/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.8% 9/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Blood alkaline phosphatase increased	10.4% 35/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Blood creatine phosphokinase MB increased	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Blood creatine phosphokinase increased	1.2% 4/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Blood creatinine increased	8.0% 27/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	4.5% 7/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Blood thyroid stimulating hormone decreased	1.8% 6/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Gamma-glutamyltransferase increased	11.9% 40/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.8% 6/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Haemoglobin decreased	2.7% 9/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	9.6% 15/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Lipase increased	11.0% 37/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Lymphocyte count decreased	2.7% 9/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	2.6% 4/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Neutrophil count decreased	6.5% 22/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	20.5% 32/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Platelet count decreased	3.0% 10/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	6.4% 10/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Weight decreased	17.5% 59/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.2% 5/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	33.3% 3/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations Weight increased	6.8% 23/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.64% 1/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Investigations White blood cell count decreased	9.5% 32/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	26.9% 42/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Decreased appetite	31.5% 106/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	33.3% 52/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	55.6% 5/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hyperglycaemia	8.3% 28/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.2% 5/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypertriglyceridaemia	0.89% 3/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hyperuricaemia	4.2% 14/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.9% 3/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypoalbuminaemia	7.7% 26/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	10.3% 16/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypocalcaemia	3.6% 12/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.8% 9/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypochloraemia	6.8% 23/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.8% 6/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypokalaemia	7.4% 25/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.1% 8/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hyponatraemia	16.3% 55/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	6.4% 10/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	33.3% 3/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypophosphataemia	2.7% 9/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Hypoproteinaemia	9.2% 31/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	9.0% 14/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Arthralgia	9.2% 31/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	4.5% 7/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Back pain	10.4% 35/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.8% 9/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Myalgia	3.6% 12/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	7.1% 11/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Musculoskeletal and connective tissue disorders Pain in extremity	3.6% 12/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	8.3% 13/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Diplegia	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Dizziness	6.5% 22/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	4.5% 7/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Headache	5.3% 18/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.9% 3/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Hypoaesthesia	4.7% 16/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	6.4% 10/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Nervous system disorders Neuropathy peripheral	0.89% 3/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.1% 8/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Psychiatric disorders Delirium	0.30% 1/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Psychiatric disorders Insomnia	7.1% 24/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	9.0% 14/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Psychiatric disorders Sleep disorder	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Renal and urinary disorders Renal impairment	1.2% 4/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Asthma	5.0% 17/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	6.4% 10/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Cough	30.9% 104/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	27.6% 43/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.7% 63/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	17.3% 27/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	22.2% 2/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	14.8% 50/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	16.7% 26/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Productive cough	13.4% 45/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	10.3% 16/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.59% 2/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	5.6% 19/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	1.3% 2/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Skin and subcutaneous tissue disorders Alopecia	3.6% 12/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	23.7% 37/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	0.00% 0/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Skin and subcutaneous tissue disorders Pruritus	11.6% 39/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	3.2% 5/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	11.1% 1/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)
Skin and subcutaneous tissue disorders Rash	16.0% 54/337 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	5.8% 9/156 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)	33.3% 3/9 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 95 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 93 months)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

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