Trial Outcomes & Findings for Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer (NCT NCT02954991)

NCT ID: NCT02954991

Last Updated: 2024-04-22

Results Overview

ORR is defined as the percentage of participants that were documented to have a confirmed complete response (CR) or partial response (PR) as defined by RECIST v1.1.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 161 participants
• Primary outcome timeframe: Up to 40.6 months
• Results posted on: 2024-04-22

Participant Flow

Participants were enrolled across 25 sites in the United States from November 2016 to November 2021.

Participants enrolled: 161, 156 included for sitravatinib + nivolumab and 5 for glesatinib + nivolumab. Main study groups: CIT Experienced and CIT Naive. Enrollment into glesatinib cohorts was discontinued November 2017. Enrollment into mocetinostat cohorts was never initiated. These decisions were not based on participant safety in Study MRTX-500.

Participant milestones

Measure	CIT Experienced: Sitravatinib and Nivolumab Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Glesatinib and Nivolumab Participants received glesatinib 500 mg oral tablets twice daily in combination with nivolumab 240 mg every 2 weeks intravenously.
Overall Study STARTED	124	32	5
Overall Study Received Any Study Treatment	124	32	5
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	124	32	5

Reasons for withdrawal

Measure	CIT Experienced: Sitravatinib and Nivolumab Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Glesatinib and Nivolumab Participants received glesatinib 500 mg oral tablets twice daily in combination with nivolumab 240 mg every 2 weeks intravenously.
Overall Study Death	92	11	2
Overall Study Lost to Follow-up	3	2	0
Overall Study Withdrawal by Subject	9	8	1
Overall Study Study Terminated by Sponsor	18	10	1
Overall Study Miscellaneous	2	1	1

Baseline Characteristics

Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=32 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Glesatinib and Nivolumab n=5 Participants Participants received glesatinib 500 mg oral tablets twice daily in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Total n=161 Participants Total of all reporting groups
Age, Customized 30 to 89 years	124 Participants n=5 Participants	32 Participants n=7 Participants	5 Participants n=5 Participants	161 Participants n=4 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	20 Participants n=7 Participants	2 Participants n=5 Participants	88 Participants n=4 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	12 Participants n=7 Participants	3 Participants n=5 Participants	73 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	118 Participants n=5 Participants	29 Participants n=7 Participants	5 Participants n=5 Participants	152 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized [Not specified] · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized [Not specified] · Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized [Not specified] · Native Hawaiin or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized [Not specified] · Black or African American	8 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized [Not specified] · White	107 Participants n=5 Participants	26 Participants n=7 Participants	3 Participants n=5 Participants	136 Participants n=4 Participants
Race/Ethnicity, Customized [Not specified] · Other	5 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 40.6 months

Population: The Full Analysis Set (FAS) was defined as all participants who received at least 1 dose of both study treatments (sitravatinib or glesatinib) and nivolumab. Data was only planned to be reported for participants in the Phase 2 study, so no data is present for the 5 participants who received glesatinib in the lead- in phase only.

ORR is defined as the percentage of participants that were documented to have a confirmed complete response (CR) or partial response (PR) as defined by RECIST v1.1.

Outcome measures

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=32 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Cycle 2 Day 15 Summary of all patients sitravatinib 120mg QD trough concentrations at C2D15	Cycle 3 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C3D1	Cycle 5 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C5D1
Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	15.3 percentage of participants Interval 9.5 to 22.9	25 percentage of participants Interval 11.5 to 43.4	—	—	—

SECONDARY outcome

Timeframe: Day 1 up to 28 days after the last dose (median time on treatment was: CIT experienced 3.7 months; CIT naïve 4.8 months)

Population: The Safety Population was defined as all participants who received at least 1 dose of any study treatment (sitravatinib, glesatinib, or nivolumab). Per statistical analysis plan, only AEs for sitravatinib + nivolumab will be summarized. TEAE tables for glesatinib + nivolumab were not produced and therefore will not be reported here.

TEAEs were defined as any event that first occur or increase in severity on or after the first dose of study treatment and not more than 28 days after the last dose of study treatment and prior to the initiation of subsequent systemic anti- cancer therapy.

Any clinically significant changes in laboratory tests were recorded as TEAEs.

Outcome measures

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=32 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Cycle 2 Day 15 Summary of all patients sitravatinib 120mg QD trough concentrations at C2D15	Cycle 3 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C3D1	Cycle 5 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C5D1
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	123 Participants	32 Participants	—	—	—

SECONDARY outcome

Timeframe: Up to 38.8 months

Population: Clinical Activity Evaluable Population was defined as all participants who received at least 1 dose of both study treatments (sitravatinib or glesatinib) and nivolumab, had an evaluable baseline tumor assessment, and ≥ 1 postbaseline tumor assessment. DOR was only calculated for the participants that achieved a confirmed CR or PR.

DOR was defined as the time in months from date of the first documentation of objective response (CR or PR) to the first documentation of objective progressive disease (PD) or to death due to any cause in the absence of documented PD. (Be aware, the population analyzed here is the Clinical Activity Evaluable Population and not the Full Analysis Set as used in outcome measure 1).

Outcome measures

Measure	CIT Experienced: Sitravatinib and Nivolumab n=19 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=8 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Cycle 2 Day 15 Summary of all patients sitravatinib 120mg QD trough concentrations at C2D15	Cycle 3 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C3D1	Cycle 5 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C5D1
Duration of Response (DOR)	11.0 months Interval 3.7 to 13.1	11.1 months Interval 3.7 to Insufficient number of participants with events	—	—	—

SECONDARY outcome

Timeframe: Up to 40.6 months

Population: The FAS was defined as all participants who received at least 1 dose of both study treatment (sitravatinib or glesatinib) and nivolumab. Data was only planned to be collected for participants in the Phase 2 study, so no data is present for the 5 participants who received glesatinib in the lead-in phase only.

PFS was defined as the time from the first dose of study drug to the date of PD or death due to any cause in the absence of documented PD, whichever occurs first.

Outcome measures

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=32 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Cycle 2 Day 15 Summary of all patients sitravatinib 120mg QD trough concentrations at C2D15	Cycle 3 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C3D1	Cycle 5 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C5D1
Progression Free Survival (PFS)	5.4 months Interval 4.2 to 5.7	7.1 months Interval 4.0 to 13.1	—	—	—

SECONDARY outcome

Timeframe: Up to 43.8 months

Population: FAS was defined as all participants who received at least 1 dose of both study treatments (sitravatinib or glesatinib) and nivolumab. Data was only planned to be collected for participants in the Phase 2 study, so no data is present for the 5 participants who received glesatinib in the lead-in phase only.

OS was defined as the time from first dose of study drug to the date of death due to any cause.

Outcome measures

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=32 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Cycle 2 Day 15 Summary of all patients sitravatinib 120mg QD trough concentrations at C2D15	Cycle 3 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C3D1	Cycle 5 Day 1 Summary of all patients sitravatinib 120mg QD trough concentrations at C5D1
Overall Survival (OS)	11.5 months Interval 8.7 to 15.0	NA months Interval 9.8 to The overall median value for CIT naive was not reached, and the upper limit of confidence interval was not estimable. Only 11 events and 21 patients censored, therefore not enough data to estimate the median survival and upper limit of 95% CI.	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 through Cycle 5 Day 1

Predose (trough) concentrations for sitravatinib

Outcome measures

Measure	CIT Experienced: Sitravatinib and Nivolumab n=117 Participants Participants who had previously received checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naïve: Sitravatinib and Nivolumab n=82 Participants Participants who had not previously received CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Cycle 2 Day 15 n=57 Participants Summary of all patients sitravatinib 120mg QD trough concentrations at C2D15	Cycle 3 Day 1 n=39 Participants Summary of all patients sitravatinib 120mg QD trough concentrations at C3D1	Cycle 5 Day 1 n=11 Participants Summary of all patients sitravatinib 120mg QD trough concentrations at C5D1
Blood Plasma Concentrations	76.57 ng/ml Standard Deviation 51.041	59.25 ng/ml Standard Deviation 36.759	52.87 ng/ml Standard Deviation 26.265	46.41 ng/ml Standard Deviation 26.183	30.04 ng/ml Standard Deviation 12.239

Adverse Events

CIT Experienced: Sitravatinib and Nivolumab

Serious events: 62 serious events

Other events: 122 other events

Deaths: 92 deaths

CIT Naive: Sitravatinib and Nivolumab

Serious events: 17 serious events

Other events: 31 other events

Deaths: 11 deaths

Glesatinib and Nivolumab

Serious events: 1 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 participants at risk Participants who had previously experienced checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naive: Sitravatinib and Nivolumab n=32 participants at risk Participants who had not previously experienced CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Glesatinib and Nivolumab n=5 participants at risk Participants received glesatinib 500 mg oral tablets twice daily in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.
Blood and lymphatic system disorders Anaemia	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Angina pectoris	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Angina unstable	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Atrial fibrillation	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Cardiac arrest	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Cardiac failure	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Myocardial infarction	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Myocarditis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Pericardial effusion	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Endocrine disorders Hypothyroidism	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Abdominal pain	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Colitis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Colitis ischaemic	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Diarrhoea	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Duodenal ulcer	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Gastric ulcer	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Gastric ulcer perforation	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Gastritis	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Ileus	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Large intestinal ulcer	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Nausea	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Pancreatitis	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Small intestinal obstruction	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Vomiting	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Asthenia	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Fatigue	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Non-cardiac chest pain	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Systemic inflammatory response syndrome	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Hepatobiliary disorders Bile duct obstruction	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Hepatobiliary disorders Cholecystitis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Immune system disorders Anaphylactic reaction	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Adrenalitis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Cystitis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Encephalitis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Gangrene	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Lung infection	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Pneumococcal sepsis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Pneumonia	8.1% 10/124 • Number of events 10 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Pneumonia viral	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Sepsis	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Urinary tract infection	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Wound infection	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Ejection fraction decreased	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Troponin increased	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Dehydration	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Failure to thrive	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hyponatraemia	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Pain in extremity	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Ataxia	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Cerebrovascular accident	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Dizziness	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Encephalopathy	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Neuralgia	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Posterior reversible encephalopathy syndrome	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Seizure	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Syncope	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Toxic encephalopathy	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Psychiatric disorders Confusional state	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Psychiatric disorders Delirium	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Renal and urinary disorders Acute kidney injury	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Aspiration	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Hypoxia	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.0% 5/124 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Decubitus ulcer	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Deep vein thrombosis	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Embolism	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Hypertension	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Hypertensive crisis	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Hypotension	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Peripheral ischaemia	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Shock haemorrhagic	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.81% 1/124 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).

Other adverse events

Measure	CIT Experienced: Sitravatinib and Nivolumab n=124 participants at risk Participants who had previously experienced checkpoint inhibitor therapy (CIT) received sitravatinib 120 mg oral capsules once daily (QD) in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	CIT Naive: Sitravatinib and Nivolumab n=32 participants at risk Participants who had not previously experienced CIT received sitravatinib 120 mg oral capsules QD in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.	Glesatinib and Nivolumab n=5 participants at risk Participants received glesatinib 500 mg oral tablets twice daily in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks intravenously.
Blood and lymphatic system disorders Anaemia	21.8% 27/124 • Number of events 27 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	34.4% 11/32 • Number of events 11 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Blood and lymphatic system disorders Thrombocytopenia	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Cardiac disorders Sinus tachycardia	9.7% 12/124 • Number of events 12 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Endocrine disorders Hyperthyroidism	4.0% 5/124 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Endocrine disorders Hypothyroidism	24.2% 30/124 • Number of events 30 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	40.6% 13/32 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Eye disorders Vision blurred	4.8% 6/124 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Abdominal distension	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Abdominal pain	18.5% 23/124 • Number of events 23 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	15.6% 5/32 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Abdominal pain lower	2.4% 3/124 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Abdominal rigidity	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Constipation	25.0% 31/124 • Number of events 31 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	37.5% 12/32 • Number of events 12 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Diarrhoea	63.7% 79/124 • Number of events 79 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	62.5% 20/32 • Number of events 20 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	60.0% 3/5 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Dry mouth	13.7% 17/124 • Number of events 17 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	15.6% 5/32 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Dyspepsia	7.3% 9/124 • Number of events 9 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Dysphagia	7.3% 9/124 • Number of events 9 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Flatulence	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Gastrooesophageal reflux disease	10.5% 13/124 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Nausea	50.0% 62/124 • Number of events 62 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	50.0% 16/32 • Number of events 16 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Stomatitis	16.1% 20/124 • Number of events 20 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Gastrointestinal disorders Vomiting	38.7% 48/124 • Number of events 48 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	37.5% 12/32 • Number of events 12 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Asthenia	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Chills	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Fatigue	62.1% 77/124 • Number of events 77 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	65.6% 21/32 • Number of events 21 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	40.0% 2/5 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Gait disturbance	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Mucosal inflammation	9.7% 12/124 • Number of events 12 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Non-cardiac chest pain	8.9% 11/124 • Number of events 11 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Oedema peripheral	13.7% 17/124 • Number of events 17 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
General disorders Pyrexia	12.1% 15/124 • Number of events 15 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Pneumonia	9.7% 12/124 • Number of events 12 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Upper respiratory tract infection	12.1% 15/124 • Number of events 15 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Infections and infestations Urinary tract infection	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Injury, poisoning and procedural complications Fall	12.1% 15/124 • Number of events 15 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Alanine aminotransferase increased	22.6% 28/124 • Number of events 28 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	40.0% 2/5 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Amylase increased	7.3% 9/124 • Number of events 9 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Aspartate aminotransferase increased	21.8% 27/124 • Number of events 27 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	40.0% 2/5 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Blood alkaline phosphatase increased	14.5% 18/124 • Number of events 18 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Blood creatinine increased	7.3% 9/124 • Number of events 9 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Blood thyroid stimulating hormone increased	4.0% 5/124 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	18.8% 6/32 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Lipase increased	11.3% 14/124 • Number of events 14 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Lymphocyte count decreased	8.9% 11/124 • Number of events 11 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Platelet count decreased	12.1% 15/124 • Number of events 15 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	15.6% 5/32 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations Weight decreased	46.0% 57/124 • Number of events 57 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	40.6% 13/32 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Investigations White blood cell count decreased	4.8% 6/124 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Decreased appetite	50.0% 62/124 • Number of events 62 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	59.4% 19/32 • Number of events 19 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Dehydration	21.0% 26/124 • Number of events 26 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hyperglycaemia	4.0% 5/124 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hyperuricaemia	8.9% 11/124 • Number of events 11 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hypoalbuminaemia	26.6% 33/124 • Number of events 33 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hypocalcaemia	12.9% 16/124 • Number of events 16 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hypoglycaemia	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hypokalaemia	18.5% 23/124 • Number of events 23 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	18.8% 6/32 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hypomagnesaemia	20.2% 25/124 • Number of events 25 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hyponatraemia	25.0% 31/124 • Number of events 31 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	31.2% 10/32 • Number of events 10 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Metabolism and nutrition disorders Hypophosphataemia	4.8% 6/124 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Arthralgia	16.1% 20/124 • Number of events 20 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	15.6% 5/32 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Back pain	16.9% 21/124 • Number of events 21 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	15.6% 5/32 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/124 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Muscle spasms	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Muscular weakness	10.5% 13/124 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Myalgia	10.5% 13/124 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Musculoskeletal and connective tissue disorders Pain in extremity	9.7% 12/124 • Number of events 12 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Dizziness	15.3% 19/124 • Number of events 19 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Dysgeusia	11.3% 14/124 • Number of events 14 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Headache	14.5% 18/124 • Number of events 18 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	18.8% 6/32 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Nervous system disorders Neuropathy peripheral	2.4% 3/124 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Psychiatric disorders Anxiety	8.1% 10/124 • Number of events 10 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Psychiatric disorders Depression	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Psychiatric disorders Insomnia	12.1% 15/124 • Number of events 15 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Renal and urinary disorders Proteinuria	11.3% 14/124 • Number of events 14 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	21.9% 7/32 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Cough	25.8% 32/124 • Number of events 32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	46.9% 15/32 • Number of events 15 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Dysphonia	33.9% 42/124 • Number of events 42 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	31.2% 10/32 • Number of events 10 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Dyspnoea	24.2% 30/124 • Number of events 30 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	31.2% 10/32 • Number of events 10 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 7/124 • Number of events 7 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.3% 14/124 • Number of events 14 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Productive cough	8.9% 11/124 • Number of events 11 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Respiratory, thoracic and mediastinal disorders Wheezing	4.0% 5/124 • Number of events 5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	9.4% 3/32 • Number of events 3 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Dry skin	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	6.2% 2/32 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	16.1% 20/124 • Number of events 20 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	25.0% 8/32 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Pruritus	7.3% 9/124 • Number of events 9 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	12.5% 4/32 • Number of events 4 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Rash	10.5% 13/124 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	18.8% 6/32 • Number of events 6 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Skin and subcutaneous tissue disorders Rash maculo-papular	10.5% 13/124 • Number of events 13 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Deep vein thrombosis	1.6% 2/124 • Number of events 2 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	3.1% 1/32 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	20.0% 1/5 • Number of events 1 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Hypertension	33.1% 41/124 • Number of events 41 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	34.4% 11/32 • Number of events 11 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).
Vascular disorders Hypotension	6.5% 8/124 • Number of events 8 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/32 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).	0.00% 0/5 • Day 1 up to 28 days after the last dose Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 46 months). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 46 months + 28 days).

Additional Information

Clinical Operations Director

Mirati Therapeutics

Phone: 858-381-5289

Email: LatvenL@Mirati.com

Results disclosure agreements

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