Trial Outcomes & Findings for Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer (NCT NCT02516241)

NCT ID: NCT02516241

Last Updated: 2026-01-28

Results Overview

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 1126 participants
• Primary outcome timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
• Results posted on: 2026-01-28

Participant Flow

Participant milestones

Measure	Combination Therapy MEDI4736 (Durvalumab) + Tremelimumab	Monotherapy MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment
Overall Study STARTED	342	346	344
Overall Study Received Treatment	340	345	313
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	342	346	344

Reasons for withdrawal

Measure	Combination Therapy MEDI4736 (Durvalumab) + Tremelimumab	Monotherapy MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment
Overall Study Death	255	262	270
Overall Study Lost to Follow-up	1	1	3
Overall Study Withdrawal by Subject	2	7	12
Overall Study participants ongoing at data cut-off	84	76	59

Baseline Characteristics

Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer

Baseline characteristics by cohort

Measure	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Total n=1032 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Ethnicity · Unknown or Not Reported	7 Participants n=158 Participants	3 Participants n=157 Participants	5 Participants n=315 Participants	15 Participants n=153 Participants
Age, Continuous Age (years)	66.4 years STANDARD_DEVIATION 9.60 • n=158 Participants	66.3 years STANDARD_DEVIATION 9.9 • n=157 Participants	67.0 years STANDARD_DEVIATION 9.32 • n=315 Participants	66.5 years STANDARD_DEVIATION 9.60 • n=153 Participants
Age, Customized Age Group (Years) · <50	19 Participants n=158 Participants	22 Participants n=157 Participants	14 Participants n=315 Participants	55 Participants n=153 Participants
Age, Customized Age Group (Years) · >= 50 - < 65	118 Participants n=158 Participants	115 Participants n=157 Participants	119 Participants n=315 Participants	352 Participants n=153 Participants
Age, Customized Age Group (Years) · >= 65 - < 75	132 Participants n=158 Participants	141 Participants n=157 Participants	137 Participants n=315 Participants	410 Participants n=153 Participants
Age, Customized Age Group (Years) · >= 75	73 Participants n=158 Participants	68 Participants n=157 Participants	74 Participants n=315 Participants	215 Participants n=153 Participants
Sex: Female, Male Sex · Female	86 Participants n=158 Participants	97 Participants n=157 Participants	70 Participants n=315 Participants	253 Participants n=153 Participants
Sex: Female, Male Sex · Male	256 Participants n=158 Participants	249 Participants n=157 Participants	274 Participants n=315 Participants	779 Participants n=153 Participants
Ethnicity (NIH/OMB) Ethnicity · Hispanic or Latino	15 Participants n=158 Participants	14 Participants n=157 Participants	17 Participants n=315 Participants	46 Participants n=153 Participants
Ethnicity (NIH/OMB) Ethnicity · Not Hispanic or Latino	320 Participants n=158 Participants	329 Participants n=157 Participants	322 Participants n=315 Participants	971 Participants n=153 Participants
Race/Ethnicity, Customized Race · White	253 Participants n=158 Participants	278 Participants n=157 Participants	260 Participants n=315 Participants	791 Participants n=153 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=158 Participants	3 Participants n=157 Participants	0 Participants n=315 Participants	6 Participants n=153 Participants
Race/Ethnicity, Customized Race · Asian	72 Participants n=158 Participants	60 Participants n=157 Participants	76 Participants n=315 Participants	208 Participants n=153 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or other Pacific islander	0 Participants n=158 Participants	0 Participants n=157 Participants	0 Participants n=315 Participants	0 Participants n=153 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=158 Participants	0 Participants n=157 Participants	0 Participants n=315 Participants	0 Participants n=153 Participants
Race/Ethnicity, Customized Race · Other	13 Participants n=158 Participants	4 Participants n=157 Participants	8 Participants n=315 Participants	25 Participants n=153 Participants
Race/Ethnicity, Customized Race · Unknown or Not Reported	1 Participants n=158 Participants	1 Participants n=157 Participants	0 Participants n=315 Participants	2 Participants n=153 Participants

PRIMARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=344 Participants MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set	12.1 Months Interval 10.9 to 14.0	—	15.1 Months Interval 13.1 to 18.0

PRIMARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=207 Participants MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=209 Participants MEDI4736 (Durvalumab) + Tremelimumab
To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set	12.1 Months Interval 10.4 to 15.0	—	14.4 Months Interval 10.4 to 17.3

SECONDARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=344 Participants MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=346 Participants MEDI4736 (Durvalumab) + Tremelimumab
OS, Full Analysis Set - Durvalumab Monotherapy vs SoC	12.1 Months Interval 10.9 to 14.0	—	13.2 Months Interval 10.3 to 15.0

SECONDARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=207 Participants MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC	12.1 Months Interval 10.4 to 15.0	—	17.9 Months Interval 14.8 to 24.2

SECONDARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy	10.9 Months Interval 8.0 to 14.8	12.2 Months Interval 10.4 to 14.0	11.8 Months Interval 8.9 to 15.8

SECONDARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Alive at 24 Months (OS24), Full Analysis Set	31.5 percentage of participants Interval 26.6 to 36.4	29.0 percentage of participants Interval 24.2 to 34.0	39.0 percentage of participants Interval 33.8 to 44.2

SECONDARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Alive at 24 Months (OS24), PD-L1-High Analysis Set	36.0 percentage of participants Interval 29.5 to 42.6	29.3 percentage of participants Interval 23.1 to 35.7	43.7 percentage of participants Interval 36.8 to 50.3

SECONDARY outcome

Timeframe: From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Alive at 24 Months (OS24), PD-L1-Low/Negative Analysis Set	24.5 percentage of participants Interval 17.6 to 32.0	28.6 percentage of participants Interval 21.2 to 36.4	32.1 percentage of participants Interval 24.5 to 40.0

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression.

Median PFS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
PFS, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC	2.3 Months Interval 1.9 to 3.5	6.7 Months Interval 5.7 to 7.3	3.7 Months Interval 3.4 to 3.8

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression.

Median PFS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
PFS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC	2.4 Months Interval 1.9 to 3.7	5.8 Months Interval 5.6 to 7.2	4.1 Months Interval 3.6 to 5.7

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression.

Median PFS was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
PFS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy	2.0 Months Interval 1.9 to 3.5	7.2 Months Interval 5.7 to 7.5	2.0 Months Interval 1.9 to 3.6

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Alive and Progression-free at 12 Months (APF12), Full Analysis Set	16.8 percentage of participants Interval 13.1 to 21.1	15.3 percentage of participants Interval 11.4 to 19.7	21.4 percentage of participants Interval 17.2 to 26.0

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Alive and Progression-free at 12 Months (APF12), PD-L1-High Analysis Set	21.2 percentage of participants Interval 15.9 to 27.0	15.0 percentage of participants Interval 10.2 to 20.7	25.6 percentage of participants Interval 19.7 to 31.8

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Alive and Progression-free at 12 Months (APF12), PD-L1-Low/Negative Analysis Set	9.7 percentage of participants Interval 5.4 to 15.7	15.6 percentage of participants Interval 9.6 to 22.9	15.2 percentage of participants Interval 9.6 to 21.8

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until first confirmed disease progression, disease then assessed per local practice until 2nd progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Time from randomization to second progression or death (PFS2) was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy or death (ie, date of PFS2 event or censoring - date of randomization +1).

Median PFS2 was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
PFS2, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC	11.9 Months Interval 8.9 to 14.6	11.5 Months Interval 10.3 to 12.8	14.6 Months Interval 11.3 to 17.8

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until first confirmed disease progression, disease then assessed per local practice until 2nd progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Time from randomization to second progression or death (PFS2) was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy or death (ie, date of PFS2 event or censoring - date of randomization +1).

Median PFS2 was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
PFS2, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC	13.4 Months Interval 9.7 to 17.5	11.3 Months Interval 8.9 to 14.3	17.2 Months Interval 12.1 to 24.8

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until first confirmed disease progression, disease then assessed per local practice until 2nd progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Time from randomization to second progression or death (PFS2) was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy or death (ie, date of PFS2 event or censoring - date of randomization +1).

Median PFS2 was calculated using the Kaplan-Meier technique.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
PFS2, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy	9.4 Months Interval 7.0 to 13.7	11.6 Months Interval 10.3 to 13.4	10.7 Months Interval 7.5 to 16.6

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Objective Response Rate (ORR), Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC	25.7 percentage of participants	49.1 percentage of participants	36.3 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Objective Response Rate (ORR), PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC	27.8 percentage of participants	48.3 percentage of participants	46.8 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Objective Response Rate (ORR), PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy	22.6 percentage of participants	50.4 percentage of participants	20.4 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (01NOV2017, a maximum of 3 years).

Population: Durvalumab Cisplatin Ineligible Population include all patients who had received D monotherapy and were not eligible for cisplatin treatment at baseline (per eCRF).

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR.

unconfirmed responses are excluded.

Outcome measures

Measure	Monotherapy n=56 Participants MEDI4736 (Durvalumab)	Standard of Care n=143 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=87 Participants MEDI4736 (Durvalumab) + Tremelimumab
Objective Response Rate (ORR) Based on BICR Assessment According to RECIST 1.1 - Responses Are Confirmed - Durvalumab Cisplatin Ineligible Population	17.9 percentage of participants	21.0 percentage of participants	23.0 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 6 months or the data cut-off date (27JAN2020).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Disease control rate (DCR) at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, i.e., 161 days), following the start of study treatment.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Disease Control Rate (DCR) at 6 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC	31.8 percentage of participants	55.5 percentage of participants	41.5 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 6 months or the data cut-off date (27JAN2020).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Disease control rate (DCR) at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, i.e., 161 days), following the start of study treatment.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Disease Control Rate (DCR) at 6 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC	34.4 percentage of participants	53.1 percentage of participants	49.8 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 6 months or the data cut-off date (27JAN2020).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Disease control rate (DCR) at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, i.e., 161 days), following the start of study treatment.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Disease Control Rate (DCR) at 6 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy	27.7 percentage of participants	59.1 percentage of participants	29.2 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020)

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Disease control rate (DCR) at 12 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, i.e., 329 days), following the start of study treatment.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Disease Control Rate (DCR) at 12 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC	28.0 percentage of participants	50.6 percentage of participants	38.0 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Disease control rate (DCR) at 12 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, i.e., 329 days), following the start of study treatment.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Disease Control Rate (DCR) at 12 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC	30.6 percentage of participants	48.8 percentage of participants	47.3 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Disease control rate (DCR) at 12 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, i.e., 329 days), following the start of study treatment.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Disease Control Rate (DCR) at 12 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy	24.1 percentage of participants	53.3 percentage of participants	24.1 percentage of participants

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Duration of response (DoR) (per RECIST 1.1 as assessed by investigator) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1).

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Duration of Response (DoR), Full Analysis Set	9.3 Months Interval 5.4 to upper limit is not reached	5.7 Months Interval 3.7 to 9.3	11.1 Months Interval 4.3 to upper limit is not reached

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

Duration of response (DoR) (per RECIST 1.1 as assessed by investigator) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1).

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Duration of Response (DoR), PD-L1-High Analysis Set	18.5 Months Interval 5.6 to upper limit is not reached.	5.8 Months Interval 3.7 to 11.5	10.0 Months Interval 3.8 to upper limit is not reached.

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Duration of response (DoR) (per RECIST 1.1 as assessed by investigator) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1).

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Duration of Response (DoR), PD-L1-Low/Negative Analysis Set	5.6 Months Interval 3.8 to upper limit is not reached.	5.7 Months Interval 3.9 to 8.2	12.9 Months Interval 5.5 to upper limit is not reached.

SECONDARY outcome

Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, pre-dose at week 4, and at follow-up Month 3.

Population: Pharmacokinetic analysis set included all patients who received at least 1 dose of durvalumab or tremelimumab per the protocol and had at least one post dose evaluable PK data of durvalumab or tremelimumab

Blood samples were collected to determine the serum concentration of durvalumab.

Outcome measures

Measure	Monotherapy n=343 Participants MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=339 Participants MEDI4736 (Durvalumab) + Tremelimumab
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 0 - Postdose	484 μg/mL Standard Deviation 162	—	511 μg/mL Standard Deviation 338
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 4 - Predose	78.9 μg/mL Standard Deviation 56.5	—	75.3 μg/mL Standard Deviation 84.4
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 12 - Predose	144 μg/mL Standard Deviation 82.5	—	125 μg/mL Standard Deviation 97.7
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 12 - Postdose	576 μg/mL Standard Deviation 233	—	594 μg/mL Standard Deviation 298
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 24 - Predose	163 μg/mL Standard Deviation 82.5	—	150 μg/mL Standard Deviation 94.4
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 24 - Postdose	600 μg/mL Standard Deviation 244	—	604 μg/mL Standard Deviation 249
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Follow-up Month 3	19.9 μg/mL Standard Deviation 18.4	—	23.3 μg/mL Standard Deviation 50
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set Week 0 - Predose	NA μg/mL Standard Deviation NA week 0 pre-dose serum concentrations are below the level of detection	—	NA μg/mL Standard Deviation NA week 0 pre-dose serum concentrations are below the level of detection

SECONDARY outcome

Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, pre-dose at week 4, and at follow-up Month 3.

Population: Pharmacokinetic analysis set included all patients who received at least 1 dose of durvalumab or tremelimumab per the protocol and had at least one post dose evaluable PK data of durvalumab or tremelimumab

Blood samples were collected to determine the serum concentration of tremelimumab.

Outcome measures

Measure	Monotherapy MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=339 Participants MEDI4736 (Durvalumab) + Tremelimumab
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set Week 0 - Predose	—	—	NA μg/mL Standard Deviation NA week 0 pre-dose serum concentrations are below the level of detection
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set Week 0 - Postdose	—	—	24.0 μg/mL Standard Deviation 11.5
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set Week 4 - Predose	—	—	3.75 μg/mL Standard Deviation 3.18
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set Week 12 - Predose	—	—	5.43 μg/mL Standard Deviation 4.01
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set Week 12 - Postdose	—	—	28.1 μg/mL Standard Deviation 13.2
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set Follow-up Month 3	—	—	0.943 μg/mL Standard Deviation 1.40

SECONDARY outcome

Timeframe: At week 0, 4, 12 and 24, and at follow-up Month 3.

Population: ADA evaluable patients is defined as patients in the safety analysis set who have a non-missing baseline ADA and at least one non-missing post-baseline result

Serum Samples will be measured for the presence of ADAs and ADA-neutralizing antibodies for Durvalumab using validated assays. Tiered analysis will be performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples will be used. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The category may include patients meeting these criteria who are ADA positive at baseline.

Outcome measures

Measure	Monotherapy n=345 Participants MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=340 Participants MEDI4736 (Durvalumab) + Tremelimumab
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients Treatment-induced ADA (Positive Post-baseline only)	10 Participants	—	28 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients ADA Positive at Baseline only	18 Participants	—	8 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients Persistently Positive	8 Participants	—	15 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients ADA evaluable patients	302 Participants	—	293 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients ADA positive at any visit (ADA Prevalence)	31 Participants	—	37 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients Treatment-emergent ADA positive (ADA Incidence)	11 Participants	—	28 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients Treatment-boosted ADA	1 Participants	—	0 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients ADA Positive Post-baseline and Positive at Baseline	3 Participants	—	1 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients Transiently Positive	5 Participants	—	14 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients nAb Positive at any visit	2 Participants	—	3 Participants

SECONDARY outcome

Timeframe: At week 0, 4, 12 and at follow-up Month 3.

Population: ADA evaluable patients is defined as patients in the safety analysis set who have a non-missing baseline ADA and at least one non-missing post-baseline result

Serum Samples will be measured for the presence of ADAs and ADA-neutralizing antibodies for Tremelimumab using validated assays. Tiered analysis will be performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples will be used. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The category may include patients meeting these criteria who are ADA positive at baseline.

Outcome measures

Measure	Monotherapy MEDI4736 (Durvalumab)	Standard of Care Standard of Care Chemotherapy Treatment	Combination Therapy n=340 Participants MEDI4736 (Durvalumab) + Tremelimumab
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients ADA evaluable patients	—	—	292 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients ADA positive at any visit (ADA Prevalence)	—	—	64 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients Treatment-emergent ADA positive (ADA Incidence)	—	—	54 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients Treatment-boosted ADA	—	—	1 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients Treatment-induced ADA (Positive Post-baseline only)	—	—	53 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients ADA Positive at Baseline only	—	—	8 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients ADA Positive Post-baseline and Positive at Baseline	—	—	3 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients Persistently Positive	—	—	31 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients Transiently Positive	—	—	25 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients nAb Positive at any visit	—	—	50 Participants

SECONDARY outcome

Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

the change from baseline in the following total/index scores will be evaluated as secondary endpoints: FACT-BL TOI (refer to as TOI), FACT-BL Total score, and NFBlSI-18 score.

All the 5 subscales (PWB (0-28), FWB (0-28), EWB (0-24), SWB (0-28), and BlCS(0-48)) are summed as the FACT-BL total score (range 0-156), while the sum of PWB, FWB and BICS constitutes the FACT-BL TOI (range 0-104).

NFBlSI-18 (range 0-72) is based on the scores of 16 items (GP4, C2, BL1, GP3, GE6, GE1, C6, BL5, GF5, GP2, GP1, GP6, C3, GP5, GF3, GF7) and 2 extra items "I feel weak all overall" and "I feel light-headed (dizzy)". The range of each item is 0-4.

Higher score represent worse outcome.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC NFBLSI - 18 Score (Average overall visits)	-3.1 Scores on a scale Standard Error 0.76	-5.2 Scores on a scale Standard Error 0.82	-3.7 Scores on a scale Standard Error 0.70
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC FACT-BL TOI (Average overall visits)	-3.9 Scores on a scale Standard Error 0.95	-7.2 Scores on a scale Standard Error 1.02	-5.5 Scores on a scale Standard Error 0.87
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC FACT-BL Total score (Average overall visits)	-4.7 Scores on a scale Standard Error 1.30	-8.8 Scores on a scale Standard Error 1.39	-7.2 Scores on a scale Standard Error 1.19

SECONDARY outcome

Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control

the change from baseline in the following total/index scores will be evaluated as secondary endpoints: FACT-BL TOI (refer to as TOI), FACT-BL Total score, and NFBlSI-18 score.

All the 5 subscales (PWB (0-28), FWB (0-28), EWB (0-24), SWB (0-28), and BlCS(0-48)) are summed as the FACT-BL total score (range 0-156), while the sum of PWB, FWB and BICS constitutes the FACT-BL TOI (range 0-104).

NFBlSI-18 (range 0-72) is based on the scores of 16 items (GP4, C2, BL1, GP3, GE6, GE1, C6, BL5, GF5, GP2, GP1, GP6, C3, GP5, GF3, GF7) and 2 extra items "I feel weak all overall" and "I feel light-headed (dizzy)". The range of each item is 0-4.

Higher score represent worse

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC NFBLSI - 18 Score (Average overall visits)	-2.0 Scores on a scale Standard Error 0.87	-5.7 Scores on a scale Standard Error 0.95	-3.9 Scores on a scale Standard Error 0.85
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC FACT-BL TOI (Average overall visits)	-2.6 Scores on a scale Standard Error 1.11	-8.0 Scores on a scale Standard Error 1.22	-5.8 Scores on a scale Standard Error 1.09
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC FACT-BL Total score (Average overall visits)	-2.7 Scores on a scale Standard Error 1.51	-10.1 Scores on a scale Standard Error 1.65	-8.0 Scores on a scale Standard Error 1.47

SECONDARY outcome

Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

the change from baseline in the following total/index scores will be evaluated as secondary endpoints: FACT-BL TOI (refer to as TOI), FACT-BL Total score, and NFBlSI-18 score.

All the 5 subscales (PWB (0-28), FWB (0-28), EWB (0-24), SWB (0-28), and BlCS(0-48)) are summed as the FACT-BL total score (range 0-156), while the sum of PWB, FWB and BICS constitutes the FACT-BL TOI (range 0-104).

NFBlSI-18 (range 0-72) is based on the scores of 16 items (GP4, C2, BL1, GP3, GE6, GE1, C6, BL5, GF5, GP2, GP1, GP6, C3, GP5, GF3, GF7) and 2 extra items "I feel weak all overall" and "I feel light-headed (dizzy)". The range of each item is 0-4.

Higher score represent worse

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC NFBLSI - 18 Score (Average overall visits)	-3.8 Scores on a scale Standard Error 1.18	-2.0 Scores on a scale Standard Error 1.16	-3.4 Scores on a scale Standard Error 1.01
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC FACT-BL TOI (Average overall visits)	-5.0 Scores on a scale Standard Error 1.39	-3.0 Scores on a scale Standard Error 1.36	-4.9 Scores on a scale Standard Error 1.18
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC FACT-BL Total score (Average overall visits)	-6.5 Scores on a scale Standard Error 1.90	-3.2 Scores on a scale Standard Error 1.86	-5.7 Scores on a scale Standard Error 1.62

SECONDARY outcome

Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Fatigue will be based on the question of "I have a lack of energy" and pain will be based on the question of "I have pain", according to GP1 and GP4 in PWB, respectively.

Improvement in fatigue is defined at least 1 point improvement from baseline using GP1 of FACT-BL.

Deterioration in pain is defined as at least 1 point deterioration from baseline using GP4 of FACT-BL.

Outcome measures

Measure	Monotherapy n=346 Participants MEDI4736 (Durvalumab)	Standard of Care n=344 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=342 Participants MEDI4736 (Durvalumab) + Tremelimumab
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Patients with improvement in fatigue	37 Participants	24 Participants	38 Participants
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Patient with deterioration in pain	130 Participants	83 Participants	142 Participants

SECONDARY outcome

Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-High analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-High as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Fatigue will be based on the question of "I have a lack of energy" and pain will be based on the question of "I have pain", according to GP1 and GP4 in PWB, respectively.

Improvement in fatigue is defined at least 1 point improvement from baseline using GP1 of FACT-BL.

Deterioration in pain is defined as at least 1 point deterioration from baseline using GP4 of FACT-BL.

Outcome measures

Measure	Monotherapy n=209 Participants MEDI4736 (Durvalumab)	Standard of Care n=207 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=205 Participants MEDI4736 (Durvalumab) + Tremelimumab
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Patients with improvement in fatigue	24 Participants	14 Participants	23 Participants
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Patient with deterioration in pain	71 Participants	51 Participants	78 Participants

SECONDARY outcome

Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Population: The PD-L1-Low/Negative analysis set will include the subset of patients in the FAS whose PD-L1 status is PD-L1-Low/negative as defined by an Immunohistochemistry (IHC) assay developed by Ventana as: \<25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control AND \<25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Fatigue will be based on the question of "I have a lack of energy" and pain will be based on the question of "I have pain", according to GP1 and GP4 in PWB, respectively.

Improvement in fatigue is defined at least 1 point improvement from baseline using GP1 of FACT-BL.

Deterioration in pain is defined as at least 1 point deterioration from baseline using GP4 of FACT-BL.

Outcome measures

Measure	Monotherapy n=137 Participants MEDI4736 (Durvalumab)	Standard of Care n=137 Participants Standard of Care Chemotherapy Treatment	Combination Therapy n=137 Participants MEDI4736 (Durvalumab) + Tremelimumab
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Patients with improvement in fatigue	13 Participants	10 Participants	15 Participants
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Patient with deterioration in pain	59 Participants	32 Participants	64 Participants

Adverse Events

Combination Therapy

Serious events: 179 serious events

Other events: 306 other events

Deaths: 255 deaths

Monotherapy

Serious events: 139 serious events

Other events: 312 other events

Deaths: 263 deaths

Standard of Care

Serious events: 125 serious events

Other events: 299 other events

Deaths: 270 deaths

Serious adverse events

Measure	Combination Therapy n=340 participants at risk MEDI4736 (Durvalumab) + Tremelimumab	Monotherapy n=345 participants at risk MEDI4736 (Durvalumab)	Standard of Care n=313 participants at risk Standard of Care Chemotherapy Treatment
Blood and lymphatic system disorders Anaemia	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.0% 7/345 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.9% 9/313 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Febrile neutropenia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Haematotoxicity	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.96% 3/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Leukopenia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.96% 3/313 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Neutropenia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Pancytopenia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.9% 6/313 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Acute coronary syndrome	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Acute myocardial infarction	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Angina pectoris	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Atrial fibrillation	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Cardiac arrest	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.96% 3/313 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Cardiac failure	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Cardiac failure acute	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Cardiac failure chronic	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Cardio-respiratory arrest	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Left ventricular dysfunction	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Myocardial infarction	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.4% 5/345 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Myocarditis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Stress cardiomyopathy	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Cardiac disorders Supraventricular tachycardia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Adrenal insufficiency	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Hyperthyroidism	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Hypophysitis	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Hypopituitarism	1.2% 4/340 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Hypothyroidism	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Thyroiditis	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Eye disorders Retinal detachment	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Abdominal hernia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Abdominal pain	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Colitis	2.1% 7/340 • Number of events 7 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Colonic fistula	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Constipation	2.1% 7/340 • Number of events 8 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Diarrhoea	4.7% 16/340 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Duodenitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Enteritis	0.59% 2/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Enterocolitis	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Enterovesical fistula	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Gastric ulcer	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Gastritis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Gastritis erosive	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Ileus	0.59% 2/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Immune-mediated enterocolitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Inguinal hernia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Intestinal obstruction	0.88% 3/340 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Large intestinal obstruction	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Large intestine perforation	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Melaena	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Nausea	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.96% 3/313 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Pancreatitis	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Pancreatitis acute	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Small intestinal obstruction	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Stomatitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Vomiting	1.5% 5/340 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Asthenia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Chest pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Death	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Extravasation	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Fatigue	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders General physical health deterioration	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Embolism	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Generalised oedema	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Hernia pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Malaise	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Mucosal inflammation	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Multiple organ dysfunction syndrome	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Non-cardiac chest pain	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Oedema peripheral	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Pyrexia	4.7% 16/340 • Number of events 19 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.7% 6/345 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.2% 13/313 • Number of events 13 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Acute hepatic failure	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Cholecystitis acute	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Cholecystitis chronic	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Cholestasis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Drug-induced liver injury	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Hepatic function abnormal	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Hepatitis	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Hepatitis cholestatic	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Hepatotoxicity	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Immune-mediated hepatitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Hepatobiliary disorders Liver abscess	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Immune system disorders Anaphylactic shock	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Immune system disorders Contrast media reaction	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Abdominal abscess	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Abscess	0.29% 1/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Amoebic dysentery	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Anal abscess	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Appendicitis	0.29% 1/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Bacteraemia	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Bronchitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Cellulitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Clostridium difficile infection	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Cystitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Device related infection	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Device related sepsis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Diverticulitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Encephalitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Enterococcal infection	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Escherichia sepsis	0.59% 2/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Escherichia urinary tract infection	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Gastroenteritis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Influenza	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Listeriosis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Lower respiratory tract infection	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Nasopharyngitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Oral herpes	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Orchitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Osteomyelitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Otitis media chronic	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Peritonitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pneumocystis jirovecii pneumonia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pneumonia	4.4% 15/340 • Number of events 15 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.3% 8/345 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pneumonia bacterial	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pneumonia pneumococcal	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Postoperative wound infection	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Prostatic abscess	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pseudomonas infection	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pyelonephritis	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.7% 6/345 • Number of events 7 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.9% 6/313 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pyelonephritis acute	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Pyelonephritis chronic	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Respiratory tract infection	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.96% 3/313 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Scrotal abscess	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Sepsis	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	3.2% 11/345 • Number of events 11 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Septic shock	0.88% 3/340 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Sinusitis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Urethritis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Urinary tract infection	6.2% 21/340 • Number of events 26 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.9% 17/345 • Number of events 23 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.7% 21/313 • Number of events 28 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Urinary tract infection bacterial	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Urinary tract infection pseudomonal	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Urosepsis	2.1% 7/340 • Number of events 8 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.2% 4/345 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Concussion	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Head injury	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Hip fracture	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Post procedural haemorrhage	0.29% 1/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Procedural complication	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Radiation pneumonitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Stoma obstruction	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Injury, poisoning and procedural complications Urostomy complication	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Alanine aminotransferase increased	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Amylase increased	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Aspartate aminotransferase increased	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Blood creatine phosphokinase increased	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Blood creatinine increased	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Blood sodium decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Cardiac murmur	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Haemoglobin decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Lipase increased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Liver function test increased	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Neutrophil count decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Oxygen saturation decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Platelet count decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.9% 6/313 • Number of events 8 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Transaminases increased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Decreased appetite	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Dehydration	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Diabetes mellitus	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Diabetic ketoacidosis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Glucose tolerance impaired	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Gout	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hypercalcaemia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hypercreatininaemia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hyperglycaemia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hypernatraemia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hypoglycaemia	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Arthritis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Autoimmune arthritis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Back pain	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Bone pain	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Flank pain	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Myopathy	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Pain in extremity	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal adenoma	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma recurrent	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Cerebellar infarction	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Cerebral haemorrhage	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Cerebral infarction	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Cerebral ischaemia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Cerebral thrombosis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Cerebrovascular accident	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Encephalopathy	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Extrapyramidal disorder	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Facial paralysis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Immune-mediated neuropathy	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Ischaemic stroke	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Lethargy	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Loss of consciousness	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Migraine	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Myasthenia gravis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Myasthenic syndrome	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Myoclonus	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Presyncope	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Somnolence	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Syncope	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Product Issues Device dislocation	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Product Issues Device occlusion	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Psychiatric disorders Completed suicide	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Psychiatric disorders Confusional state	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Psychiatric disorders Delirium	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Psychiatric disorders Depression	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Psychiatric disorders Psychotic disorder	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Acute kidney injury	1.8% 6/340 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.4% 5/345 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.6% 8/313 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Azotaemia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Bladder pain	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Bladder tamponade	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Chronic kidney disease	0.29% 1/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Cystitis noninfective	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Dysuria	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Haematuria	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Hydronephrosis	1.2% 4/340 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Nephritis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Nephrolithiasis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Obstructive nephropathy	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Oliguria	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Postrenal failure	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Renal failure	1.2% 4/340 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Renal impairment	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Renal vein thrombosis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Ureteric obstruction	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Urinary bladder rupture	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Urinary tract obstruction	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Reproductive system and breast disorders Penile haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Reproductive system and breast disorders Penile pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.2% 4/340 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Diaphragmatic paralysis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.4% 5/345 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.5% 5/340 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.2% 4/340 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.87% 3/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.9% 6/313 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Skin and subcutaneous tissue disorders Rash	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Circulatory collapse	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Deep vein thrombosis	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.64% 2/313 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Extremity necrosis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Hypertensive emergency	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Hypertensive urgency	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Hypotension	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Intermittent claudication	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Peripheral artery thrombosis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Vasculitis	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).

Other adverse events

Measure	Combination Therapy n=340 participants at risk MEDI4736 (Durvalumab) + Tremelimumab	Monotherapy n=345 participants at risk MEDI4736 (Durvalumab)	Standard of Care n=313 participants at risk Standard of Care Chemotherapy Treatment
Blood and lymphatic system disorders Anaemia	15.0% 51/340 • Number of events 53 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	16.8% 58/345 • Number of events 63 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	52.1% 163/313 • Number of events 222 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Leukopenia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.0% 25/313 • Number of events 50 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Neutropenia	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	28.4% 89/313 • Number of events 187 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Blood and lymphatic system disorders Thrombocytopenia	0.29% 1/340 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.0% 7/345 • Number of events 10 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	15.0% 47/313 • Number of events 64 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Ear and labyrinth disorders Tinnitus	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.1% 19/313 • Number of events 22 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Hyperthyroidism	6.2% 21/340 • Number of events 22 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.9% 10/345 • Number of events 10 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.32% 1/313 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Endocrine disorders Hypothyroidism	9.1% 31/340 • Number of events 34 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.7% 23/345 • Number of events 23 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/313 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Abdominal pain	12.1% 41/340 • Number of events 47 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	10.7% 37/345 • Number of events 50 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.6% 27/313 • Number of events 31 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Abdominal pain upper	5.6% 19/340 • Number of events 24 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.2% 4/345 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.6% 8/313 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Constipation	23.2% 79/340 • Number of events 88 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	19.1% 66/345 • Number of events 73 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	28.4% 89/313 • Number of events 113 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Diarrhoea	29.1% 99/340 • Number of events 146 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	18.3% 63/345 • Number of events 96 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	17.6% 55/313 • Number of events 78 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Dry mouth	6.8% 23/340 • Number of events 25 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.9% 17/345 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Dyspepsia	3.5% 12/340 • Number of events 12 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	3.5% 12/345 • Number of events 14 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.8% 18/313 • Number of events 20 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Nausea	17.1% 58/340 • Number of events 65 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	21.4% 74/345 • Number of events 88 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	45.7% 143/313 • Number of events 237 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Gastrointestinal disorders Vomiting	16.5% 56/340 • Number of events 66 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	10.4% 36/345 • Number of events 46 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	15.3% 48/313 • Number of events 61 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Asthenia	15.9% 54/340 • Number of events 69 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	11.6% 40/345 • Number of events 49 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	21.7% 68/313 • Number of events 106 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Fatigue	26.2% 89/340 • Number of events 106 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	28.4% 98/345 • Number of events 107 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	32.3% 101/313 • Number of events 127 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Malaise	1.5% 5/340 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.2% 4/345 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.1% 19/313 • Number of events 21 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Oedema peripheral	8.8% 30/340 • Number of events 39 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	10.4% 36/345 • Number of events 41 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.6% 27/313 • Number of events 33 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
General disorders Pyrexia	17.6% 60/340 • Number of events 80 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	14.5% 50/345 • Number of events 66 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	13.7% 43/313 • Number of events 63 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Nasopharyngitis	4.4% 15/340 • Number of events 16 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.2% 18/345 • Number of events 24 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	3.5% 11/313 • Number of events 13 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Infections and infestations Urinary tract infection	15.9% 54/340 • Number of events 69 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	16.8% 58/345 • Number of events 82 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	14.7% 46/313 • Number of events 57 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Alanine aminotransferase increased	4.1% 14/340 • Number of events 15 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.5% 19/345 • Number of events 21 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.7% 21/313 • Number of events 24 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Aspartate aminotransferase increased	5.0% 17/340 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.3% 15/345 • Number of events 15 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.1% 16/313 • Number of events 21 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Blood alkaline phosphatase increased	5.0% 17/340 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.8% 20/345 • Number of events 22 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.6% 8/313 • Number of events 10 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Blood creatinine increased	5.0% 17/340 • Number of events 25 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	7.8% 27/345 • Number of events 33 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	9.9% 31/313 • Number of events 37 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Lipase increased	6.8% 23/340 • Number of events 29 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.2% 18/345 • Number of events 33 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.3% 4/313 • Number of events 6 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Neutrophil count decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.29% 1/345 • Number of events 1 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	17.6% 55/313 • Number of events 135 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Platelet count decreased	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.2% 4/345 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	17.6% 55/313 • Number of events 124 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations Weight decreased	9.7% 33/340 • Number of events 34 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.1% 21/345 • Number of events 22 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.8% 18/313 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Investigations White blood cell count decreased	0.00% 0/340 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.00% 0/345 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	9.3% 29/313 • Number of events 56 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Decreased appetite	21.2% 72/340 • Number of events 79 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	19.1% 66/345 • Number of events 74 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	25.6% 80/313 • Number of events 102 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hyperglycaemia	5.3% 18/340 • Number of events 19 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.6% 9/345 • Number of events 12 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	3.2% 10/313 • Number of events 15 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hyperkalaemia	5.0% 17/340 • Number of events 20 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.2% 18/345 • Number of events 24 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.8% 18/313 • Number of events 27 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Metabolism and nutrition disorders Hypomagnesaemia	2.4% 8/340 • Number of events 10 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	6.7% 21/313 • Number of events 25 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Arthralgia	12.4% 42/340 • Number of events 56 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	10.4% 36/345 • Number of events 45 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	3.5% 11/313 • Number of events 14 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Back pain	10.0% 34/340 • Number of events 38 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	11.9% 41/345 • Number of events 46 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	9.9% 31/313 • Number of events 34 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 18/340 • Number of events 21 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	7.2% 25/345 • Number of events 28 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	7.0% 22/313 • Number of events 23 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Dizziness	7.9% 27/340 • Number of events 30 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.3% 15/345 • Number of events 21 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.0% 25/313 • Number of events 32 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Dysgeusia	2.4% 8/340 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.9% 10/345 • Number of events 10 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.3% 26/313 • Number of events 30 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Headache	5.9% 20/340 • Number of events 28 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.2% 18/345 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.1% 16/313 • Number of events 19 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Nervous system disorders Neuropathy peripheral	0.88% 3/340 • Number of events 3 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.4% 5/345 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.1% 16/313 • Number of events 17 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Psychiatric disorders Insomnia	7.4% 25/340 • Number of events 29 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	7.2% 25/345 • Number of events 25 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.5% 14/313 • Number of events 15 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Renal and urinary disorders Haematuria	10.6% 36/340 • Number of events 40 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	11.3% 39/345 • Number of events 48 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.5% 14/313 • Number of events 15 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Cough	13.5% 46/340 • Number of events 55 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	10.1% 35/345 • Number of events 41 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.8% 18/313 • Number of events 20 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.1% 24/340 • Number of events 25 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.7% 30/345 • Number of events 32 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.6% 27/313 • Number of events 30 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Hiccups	0.59% 2/340 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	0.58% 2/345 • Number of events 2 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	7.3% 23/313 • Number of events 33 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Respiratory, thoracic and mediastinal disorders Productive cough	5.9% 20/340 • Number of events 23 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.4% 5/345 • Number of events 5 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	3.2% 10/313 • Number of events 10 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Skin and subcutaneous tissue disorders Alopecia	2.6% 9/340 • Number of events 9 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	1.2% 4/345 • Number of events 4 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	10.5% 33/313 • Number of events 33 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Skin and subcutaneous tissue disorders Pruritus	27.4% 93/340 • Number of events 134 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	15.4% 53/345 • Number of events 71 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.5% 14/313 • Number of events 22 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Skin and subcutaneous tissue disorders Rash	17.1% 58/340 • Number of events 77 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	8.7% 30/345 • Number of events 38 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	4.8% 15/313 • Number of events 18 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).
Vascular disorders Hypertension	5.6% 19/340 • Number of events 20 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	5.5% 19/345 • Number of events 20 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).	2.6% 8/313 • Number of events 8 • From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).

Additional Information

Medical Science Director

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

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