Trial Outcomes & Findings for A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting (NCT NCT01808573)

NCT ID: NCT01808573

Last Updated: 2021-06-11

Results Overview

Progression Free Survival (PFS), Measured in Months, for Randomized Subjects of the Central Assessment. The time interval from the date of randomization until the first date on which recurrence, progression (per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1), or death due to any cause, is documented. For subjects without recurrence, progression or death, it is censored at the last valid tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 24 months.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 621 participants
• Primary outcome timeframe: From randomization date to recurrence, progression or death, assessed up to 38 months. The result is based on primary analysis data cut.
• Results posted on: 2021-06-11

Participant Flow

Participant milestones

Measure	Neratinib Plus Capecitabine neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Overall Study STARTED	307	314
Overall Study Received Treatment	303	311
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	307	314

Reasons for withdrawal

Measure	Neratinib Plus Capecitabine neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Overall Study Death	212	240
Overall Study Withdrawal by Subject	12	10
Overall Study Lost to Follow-up	3	0
Overall Study Discontinuation of study by sponsor	79	64
Overall Study Randomized in Error	1	0

Baseline Characteristics

A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting

Baseline characteristics by cohort

Measure	Neratinib Plus Capecitabine n=307 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=314 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Total n=621 Participants Total of all reporting groups
Age, Continuous	55.04 years STANDARD_DEVIATION 11.37 • n=5 Participants	54.32 years STANDARD_DEVIATION 11.36 • n=7 Participants	54.67 years STANDARD_DEVIATION 11.36 • n=5 Participants
Sex: Female, Male Female	307 Participants n=5 Participants	311 Participants n=7 Participants	618 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=5 Participants	42 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	256 Participants n=5 Participants	259 Participants n=7 Participants	515 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	109 Participants n=5 Participants	105 Participants n=7 Participants	214 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	9 Participants n=5 Participants	15 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	178 Participants n=5 Participants	177 Participants n=7 Participants	355 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown/Missing	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Previous HER2 Regimens 2	215 Participants n=5 Participants	215 Participants n=7 Participants	430 Participants n=5 Participants
Previous HER2 Regimens >=3	92 Participants n=5 Participants	99 Participants n=7 Participants	191 Participants n=5 Participants
Disease Location Non Visceral	60 Participants n=5 Participants	61 Participants n=7 Participants	121 Participants n=5 Participants
Disease Location Visceral	247 Participants n=5 Participants	253 Participants n=7 Participants	500 Participants n=5 Participants
Hormone Receptor Status Negative	126 Participants n=5 Participants	128 Participants n=7 Participants	254 Participants n=5 Participants
Hormone Receptor Status Positive	181 Participants n=5 Participants	186 Participants n=7 Participants	367 Participants n=5 Participants
Geographic Region Europe	121 Participants n=5 Participants	123 Participants n=7 Participants	244 Participants n=5 Participants
Geographic Region North America	59 Participants n=5 Participants	65 Participants n=7 Participants	124 Participants n=5 Participants
Geographic Region Rest of World	127 Participants n=5 Participants	126 Participants n=7 Participants	253 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization date to recurrence, progression or death, assessed up to 38 months. The result is based on primary analysis data cut.

Population: Randomized ITT Population

Progression Free Survival (PFS), Measured in Months, for Randomized Subjects of the Central Assessment. The time interval from the date of randomization until the first date on which recurrence, progression (per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1), or death due to any cause, is documented. For subjects without recurrence, progression or death, it is censored at the last valid tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 24 months.

Outcome measures

Measure	Neratinib Plus Capecitabine n=307 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=314 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Centrally Assessed Progression Free Survival	8.8 months Interval 7.8 to 9.8	6.6 months Interval 5.9 to 7.4

PRIMARY outcome

Timeframe: From randomization date to death, assessed up to 59 months.The result is based on primary analysis data cut.

Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 48 months.

Outcome measures

Measure	Neratinib Plus Capecitabine n=307 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=314 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Overall Survival	24.0 months Interval 22.1 to 25.9	22.2 months Interval 20.4 to 24.0

SECONDARY outcome

Timeframe: From randomization date to first intervention for symptomatic metastatic CNS disease, assessed up to 59 months.The result is based on primary analysis data cut.

Intervention for symptomatic metastatic central nervous system disease is defined as the time from randomization to the first start date of an intervention for symptomatic metastatic CNS disease. Subjects that do not have an intervention for symptomatic metastatic CNS and do not die will be censored at the last date known alive on or prior to the data cutoff. Deaths are treated as competing events. Percentage of participants with intervention for CNS, estimated by cumulative incidence methods. Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring.

Outcome measures

Measure	Neratinib Plus Capecitabine n=307 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=314 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Intervention for Symptomatic Metastatic Central Nervous System Disease	22.76 percentage of participants Interval 15.48 to 30.91	29.19 percentage of participants Interval 22.54 to 36.14

SECONDARY outcome

Timeframe: From randomization date to first confirmed Complete or Partial Response, whichever came earlier, up to 42 months.The result is based on primary analysis data cut.

Objective response rate is defined as the percentage of participants demonstrating an objective response during the study. Objective response includes confirmed complete responses (CR) and partial responses (PR) as defined in the RECIST criteria included in the study protocol. The ORR is for Central Assessment for subjects that had measurable disease at screening. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure	Neratinib Plus Capecitabine n=256 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=270 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Objective Response Rate (ORR) - Central Assessment (ITT Population With Measurable Disease at Screening)	32.8 percentage of participants Interval 27.1 to 38.9	26.7 percentage of participants Interval 21.5 to 32.4

SECONDARY outcome

Timeframe: From randomization date to either first confirmed CR or PR or Stable Disease, whichever came earlier, up to 42 months.The result is based on primary analysis data cut.

Clinical benefit rate is the percentage of participants who achieve overall tumor response (confirmed CR or PR) or stable disease (SD) lasting for at least 24 weeks from randomization. The CBR was for Central Assessment for subjects who had Measurable Disease at Screening.

Outcome measures

Measure	Neratinib Plus Capecitabine n=256 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=270 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Clinical Benefit Rate (CBR) - Central Assessment (ITT Population With Measurable Disease at Screening)	44.5 percentage of participants Interval 38.3 to 50.8	35.6 percentage of participants Interval 29.8 to 41.6

SECONDARY outcome

Timeframe: From start date of response after randomization to first PD, up to 33 months.The result is based on primary analysis data cut.

The Duration of Response (DOR) is for Central Assessment for the Population that Had a Response with Measurable Disease at Screening.

Duration of response is measured from the time at which measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per RECIST v1.1. This value is censored at the last valid tumor assessment if PD or death has not been documented.

Outcome measures

Measure	Neratinib Plus Capecitabine n=84 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=72 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Duration of Response (DOR) - Central Assessment (Population That Had a Response With Measurable Disease at Screening)	8.54 months Interval 5.62 to 11.17	5.55 months Interval 4.21 to 6.41

SECONDARY outcome

Timeframe: From first dose through last dose + 28 days, up to 41 months. The result is based on final data cut.

Population: Safety population: Participants receiving at least 1 dose of investigational product.

Adverse Events to be measured are Treatment-Emergent and Serious AEs that occurred on or after first dose of investigational product and up to 28 days after the last dose

Outcome measures

Measure	Neratinib Plus Capecitabine n=303 Participants neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=311 Participants lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) All Treatment-Emergent Adverse Events	99.7 percentage of participants	99.4 percentage of participants
Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) Serious Treatment-Emergent Adverse Events	34.0 percentage of participants	29.9 percentage of participants

Adverse Events

Neratinib Plus Capecitabine

Serious events: 103 serious events

Other events: 301 other events

Deaths: 219 deaths

Lapatinib Plus Capecitabine

Serious events: 93 serious events

Other events: 309 other events

Deaths: 243 deaths

Serious adverse events

Measure	Neratinib Plus Capecitabine n=303 participants at risk neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=311 participants at risk lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Blood and lymphatic system disorders Anaemia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Blood and lymphatic system disorders Febrile neutropenia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.96% 3/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Blood and lymphatic system disorders Neutropenia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Acute myocardial infarction	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Atrial fibrillation	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Cardiac arrest	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Cardiac tamponade	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Cardiomyopathy	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Palpitations	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Pericardial effusion	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Cardiac disorders Tachycardia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Ear and labyrinth disorders Vertigo	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Eye disorders Chorioretinopathy	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Abdominal distension	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Abdominal pain	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.6% 5/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Abdominal pain upper	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Ascites	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Constipation	0.99% 3/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Diarrhoea	7.3% 22/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	4.2% 13/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Gastric ulcer	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Gastritis	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Nausea	2.3% 7/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.9% 6/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Pancreatitis	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Pancreatitis acute	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Stomatitis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Varices oesophageal	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Vomiting	3.0% 9/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.9% 6/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Abasia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Asthenia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Chest pain	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Fatigue	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders General physical health deterioration	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Malaise	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Multiple organ dysfunction syndrome	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Non-cardiac chest pain	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Oedema	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Pyrexia	0.99% 3/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Suprapubic pain	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Hepatobiliary disorders Bile duct obstruction	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Hepatobiliary disorders Hepatic failure	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Hepatobiliary disorders Hepatic mass	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Hepatobiliary disorders Hepatitis fulminant	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Hepatobiliary disorders Jaundice	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Hepatobiliary disorders Jaundice cholestatic	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Immune system disorders Hypersensitivity	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Abdominal infection	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Atypical pneumonia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Bacteraemia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Catheter site infection	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Cellulitis	1.3% 4/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.6% 5/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Enterocolitis infectious	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Epiglottitis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Erysipelas	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Gastroenteritis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Influenza	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Lung infection	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Paronychia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Pneumonia	2.0% 6/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.6% 5/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Pneumonia bacterial	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Respiratory tract infection	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Sepsis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.3% 4/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Septic shock	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Soft tissue infection	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Streptococcal sepsis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Tooth infection	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Upper respiratory tract infection	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Urinary tract infection	0.99% 3/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Urosepsis	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Wound infection	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Fall	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Femur fracture	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Fracture	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Head injury	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Hip fracture	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Humerus fracture	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Injury, poisoning and procedural complications Seroma	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Blood bilirubin increased	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.96% 3/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Blood potassium increased	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Liver function test increased	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Weight decreased	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Decreased appetite	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Dehydration	1.3% 4/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.6% 5/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Hypercalcaemia	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Hypokalaemia	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.3% 4/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Back pain	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Pain in extremity	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.3% 4/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intracranial tumour haemorrhage	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	2.0% 6/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Spinal cord oedema	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericarditis malignant	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour compression	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Amnesia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Aphasia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Ataxia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Brain oedema	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Cerebellar syndrome	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Cerebral haematoma	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Cerebral infarction	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Cerebrovascular accident	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Dizziness	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Haemorrhage intracranial	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Headache	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	1.9% 6/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Hemiparesis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Hypoaesthesia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Intracranial pressure increased	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Lethargy	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Nerve root compression	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Neurological decompensation	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Neuropathy peripheral	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Paraparesis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Presyncope	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Seizure	1.3% 4/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.96% 3/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Syncope	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Tonic convulsion	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Psychiatric disorders Confusional state	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Psychiatric disorders Delirium	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Psychiatric disorders Disorientation	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Psychiatric disorders Mental status changes	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Renal and urinary disorders Acute kidney injury	2.3% 7/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Renal and urinary disorders Hydronephrosis	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Renal and urinary disorders Renal failure	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Reproductive system and breast disorders Vaginal haemorrhage	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.96% 3/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 10/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	3.5% 11/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.66% 2/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	2.3% 7/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.00% 0/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.33% 1/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Skin necrosis	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Vascular disorders Hypotension	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.64% 2/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Vascular disorders Shock	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Vascular disorders Vena cava thrombosis	0.00% 0/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	0.32% 1/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.

Other adverse events

Measure	Neratinib Plus Capecitabine n=303 participants at risk neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.	Lapatinib Plus Capecitabine n=311 participants at risk lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
Blood and lymphatic system disorders Anaemia	14.9% 45/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	16.1% 50/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Blood and lymphatic system disorders Neutropenia	7.6% 23/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	5.1% 16/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Abdominal distension	8.3% 25/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	2.9% 9/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Abdominal pain	12.2% 37/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	13.5% 42/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Abdominal pain upper	5.9% 18/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	9.0% 28/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Constipation	31.4% 95/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	12.9% 40/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Diarrhoea	81.8% 248/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	65.9% 205/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Dry mouth	5.0% 15/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	5.8% 18/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Dyspepsia	6.6% 20/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	9.3% 29/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Nausea	53.1% 161/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	41.8% 130/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Stomatitis	20.8% 63/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	26.7% 83/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Gastrointestinal disorders Vomiting	45.5% 138/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	30.5% 95/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Asthenia	11.9% 36/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	10.9% 34/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Fatigue	33.7% 102/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	31.2% 97/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Oedema peripheral	5.3% 16/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	6.8% 21/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
General disorders Pyrexia	10.6% 32/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	10.3% 32/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Paronychia	11.6% 35/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	15.8% 49/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Upper respiratory tract infection	8.6% 26/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	4.5% 14/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Urinary tract infection	8.9% 27/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	3.9% 12/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Infections and infestations Viral upper respiratory tract infection	6.6% 20/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	7.4% 23/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Alanine aminotransferase increased	8.9% 27/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	7.1% 22/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Aspartate aminotransferase increased	9.6% 29/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	9.0% 28/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Blood bilirubin increased	5.9% 18/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	10.9% 34/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Investigations Weight decreased	19.8% 60/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	13.2% 41/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Decreased appetite	35.3% 107/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	21.5% 67/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Dehydration	4.6% 14/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	5.1% 16/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Metabolism and nutrition disorders Hypokalaemia	11.6% 35/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	13.2% 41/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Arthralgia	9.6% 29/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	6.4% 20/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Back pain	9.9% 30/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	7.1% 22/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.3% 19/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	4.5% 14/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 25/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	6.8% 21/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Dizziness	14.2% 43/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	9.6% 30/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Dysgeusia	5.6% 17/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	4.2% 13/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Nervous system disorders Headache	10.6% 32/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	16.1% 50/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Psychiatric disorders Insomnia	6.6% 20/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	7.4% 23/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Cough	13.5% 41/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	10.9% 34/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.3% 19/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	8.4% 26/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.3% 13/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	6.4% 20/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Dermatitis acneiform	4.3% 13/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	7.4% 23/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Dry skin	6.6% 20/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	4.8% 15/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	45.9% 139/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	56.3% 175/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Pruritus	8.6% 26/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	8.0% 25/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Rash	10.2% 31/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	22.2% 69/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Skin fissures	3.0% 9/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	6.1% 19/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.3% 7/303 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.	5.5% 17/311 • From time of first dose, through 28 days after last dose, assessed up to 41 months. Safety population: Participants receiving at least 1 dose of investigational product. All-Cause Mortality was monitored/assessed for all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the safety population For All-Cause Mortality and Serious/Other Adverse Events, the result is based on final data cut.

Additional Information

Senior Director, Clinical Operations

Puma Biotechnology, Inc.

Phone: 424-248-6500

Email: clinicaltrials@pumabiotechnology.com

Results disclosure agreements

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