Trial Outcomes & Findings for A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069) (NCT NCT01782131)

NCT ID: NCT01782131

Last Updated: 2024-01-18

Results Overview

The percentage of participants who died with posaconazole (POS) compared to voriconazole (VOR) in the first line treatment of invasive aspergillosis (IA) in the Intention to Treat (ITT) population through Day 42 was assessed.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 585 participants
• Primary outcome timeframe: Up to ~42 days
• Results posted on: 2024-01-18

Participant Flow

After a screening phase of up to 7 days, 585 participants were enrolled/randomized, but only 575 began treatment (288 in the posaconazole [POS] group and 287 in the voriconazole [VOR] group).

Participant milestones

Measure	Posaconazole Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Overall Study STARTED	293	292
Overall Study Treated	288	287
Overall Study COMPLETED	184	177
Overall Study NOT COMPLETED	109	115

Reasons for withdrawal

Measure	Posaconazole Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Overall Study Death	93	96
Overall Study Lost to Follow-up	1	3
Overall Study Withdrawal by Subject	10	10
Overall Study Randomized but not treated	5	5
Overall Study Reason not provided	0	1

Baseline Characteristics

A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069)

Baseline characteristics by cohort

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Total n=575 Participants Total of all reporting groups
Age, Continuous	53.5 years STANDARD_DEVIATION 16.7 • n=5 Participants	53.0 years STANDARD_DEVIATION 15.9 • n=7 Participants	53.3 years STANDARD_DEVIATION 16.3 • n=5 Participants
Sex: Female, Male Female	116 Participants n=5 Participants	115 Participants n=7 Participants	231 Participants n=5 Participants
Sex: Female, Male Male	172 Participants n=5 Participants	172 Participants n=7 Participants	344 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	48 Participants n=5 Participants	57 Participants n=7 Participants	105 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	220 Participants n=5 Participants	219 Participants n=7 Participants	439 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants	11 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Asian	62 Participants n=5 Participants	60 Participants n=7 Participants	122 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	194 Participants n=5 Participants	192 Participants n=7 Participants	386 Participants n=5 Participants
Race (NIH/OMB) More than one race	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to ~42 days

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

The percentage of participants who died with posaconazole (POS) compared to voriconazole (VOR) in the first line treatment of invasive aspergillosis (IA) in the Intention to Treat (ITT) population through Day 42 was assessed.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Who Died Through Day 42 in the Intention to Treat Population	15.3 Percentage of Participants	20.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~42 days

Population: The analysis population consisted of all randomized participants who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions) and received at least one dose of study drug.

The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the Full Analysis Set (FAS) population through Day 42 was assessed.

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Who Died Through Day 42 in the Full Analysis Set Population	19.0 Percentage of Participants	18.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~84 days

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the ITT population through Day 84 was assessed.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Who Died Through Day 84 in the ITT Population	28.1 Percentage of Participants	30.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~ 84 days

Population: The analysis population consisted of all randomized participants who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions) and received at least one dose of study drug.

The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the FAS population through Day 84 was assessed.

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Who Died Through Day 84 in the FAS Population	34.4 Percentage of Participants	31.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 12 weeks (± 4 weeks)

Population: The analysis population consisted of all randomized participants who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions) and received at least one dose of study drug.

The global clinical response of POS compared to VOR in the first line treatment of invasive aspergillosis (IA) was assessed. The percentage of participants achieving adjudicated global clinical response (complete or partial) at Week 12 was reported. Complete response was classified as survival with resolution of fungal disease evidence; Partial response was survival and improvement of fungal disease.

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Achieving Global Clinical Response at Week 12 in the FAS Population	42.3 Percentage of Participants	46.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 6 weeks (± 2 weeks)

Population: The analysis population consisted of all randomized participants who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions) and received at least one dose of study drug.

The global clinical response of POS compared to VOR in the first line treatment of invasive aspergillosis (IA) was assessed. The percentage of participants achieving adjudicated global clinical response (complete or partial) at Week 6 was reported. Complete response was classified as survival with resolution of fungal disease evidence; Partial response was survival and improvement of fungal disease.

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Achieving Global Clinical Response at Week 6 in the FAS Population	44.8 Percentage of Participants	45.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~16 weeks (± 2 weeks)

Population: The analysis population consisted of all randomized participants who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions) and received at least one dose of study drug.

The number of participants experiencing mortality at Day 42, Day 84 and Day 114 in participants with proven or probable IA receiving POS versus VOR were assessed. The Kaplan-Meier estimate reports the number of participants who experienced death (all causes) through Day 114 or ~16 weeks. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). For Day 42 and Day 84, missing or 'unable to determine' responses were considered as failures (dead).

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Number of Participants Experiencing Mortality at Day 42, Day 84, and Day 114 in the FAS Population (Kaplan-Meier Time To Death Estimate) Day 42 (missing responses were included as dead)	31 Participants	32 Participants
Number of Participants Experiencing Mortality at Day 42, Day 84, and Day 114 in the FAS Population (Kaplan-Meier Time To Death Estimate) Day 84 (missing responses were included as dead)	56 Participants	53 Participants
Number of Participants Experiencing Mortality at Day 42, Day 84, and Day 114 in the FAS Population (Kaplan-Meier Time To Death Estimate) Day 114	64 Participants	56 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: All randomized participants who died by Day 42 and who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions), and received at least one dose of study drug.

The number of participants who died due to IA receiving POS versus VOR through Day 42 was assessed.

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Number of Participants Who Died Due to Invasive Aspergillosis Through Day 42 in the FAS Population	16 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to 84 days

Population: All randomized participants who died by Day 84 and who have been classified as having proven or probable IA (based upon independent adjudication assessment using the modified 2008 European Organization for Research and Treatment of Cancer/Mycoses study group \[EORTC/MSG\] definitions), and received at least one dose of study drug.

The number of participants who died due to IA receiving POS versus VOR in the FAS population through Day 84 was assessed.

Outcome measures

Measure	Posaconazole n=163 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=171 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Number of Participants Who Died Due to Invasive Aspergillosis Through Day 84 in the FAS Population	22 Participants	14 Participants

SECONDARY outcome

Timeframe: Up to ~16 weeks (± 2 weeks)

Population: The analysis population consisted of all participants who received at least one dose of study treatment.

The percentage of participants with Tier 1 treatment-emergent adverse events (TEAEs) was determined. The Tier 1 TEAEs included hepatic safety (elevated aspartate serum transaminase [AST] or alanine serum transaminase [ALT] value ≥3x upper limit of normal (ULN) and an elevated total bilirubin value ≥2x ULN and, at the same time, an alkaline phosphatase value <2 ULN); central nervous system (CNS) and visual disturbances (eye disorders, nervous system disorders, psychiatric disorders), dermatologic reactions, and adrenal insufficiency or temporally associated TEAEs of hypotension.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants With Tier 1 Treatment Emergent Adverse Events Abnormal Hepatic Laboratory Value	3.8 Percentage of Participants	3.5 Percentage of Participants
Percentage of Participants With Tier 1 Treatment Emergent Adverse Events CNS and Visual Disturbances	32.3 Percentage of Participants	35.9 Percentage of Participants
Percentage of Participants With Tier 1 Treatment Emergent Adverse Events Dermatologic Reactions	16.3 Percentage of Participants	19.2 Percentage of Participants
Percentage of Participants With Tier 1 Treatment Emergent Adverse Events Adrenal Insufficiency or Temporal Hypotension	8.0 Percentage of Participants	7.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~16 weeks (± 2 weeks)

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants With at Least One Adverse Event	97.6 Percentage of Participants	97.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~16 weeks (± 2 weeks)

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants With at Least One Drug Related Adverse Event	29.9 Percentage of Participants	40.1 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~16 weeks (± 2 weeks)

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

A serious adverse event (SAE) was an AE that resulted in death, was life threatening, required or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was another important medical event deemed such by medical or scientific judgment.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants With at Least One Serious Adverse Event	61.8 Percentage of Participants	59.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~16 weeks (± 2 weeks)

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

An SAE was an AE that resulted in death, was life threatening, required or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was another important medical event deemed such by medical or scientific judgment.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants With at Least One Serious Drug Related Adverse Event	5.6 Percentage of Participants	7.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to ~12 weeks

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

An AE was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 Participants Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event	32.3 Percentage of Participants	35.5 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, and at pre-dose on Day 7, Week 2, Week 4, Week 6, and Week 12

Population: The analysis population consisted of all randomized participants in the POS group only who received at least one dose of study treatment. Per protocol, the VOR group was not included in the analysis population because the food intake evaluation was limited to the POS group.

The characterization of the pharmacokinetics (PK) parameters of POS was determined from plasma samples taken at steady-state after receiving oral tablet of POS. Steady-state Cavg, where Cavg is defined as area under the concentration time-curve from 0 to 24 hours (AUC0-24hr) divided by the dosing interval. Data is presented in POS group column only. No evaluation of food intake on the VOR capsule was presented.

Outcome measures

Measure	Posaconazole n=288 Participants Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Steady State Average Concentration (Cavg) of Posaconazole With Food Intake Week 1	1625 ng/mL Standard Deviation 902.9	—
Steady State Average Concentration (Cavg) of Posaconazole With Food Intake Week 2	1992 ng/mL Standard Deviation 1190	—
Steady State Average Concentration (Cavg) of Posaconazole With Food Intake Week 4	1994 ng/mL Standard Deviation 956.3	—
Steady State Average Concentration (Cavg) of Posaconazole With Food Intake Week 6	2005 ng/mL Standard Deviation 1333	—
Steady State Average Concentration (Cavg) of Posaconazole With Food Intake Week 12	2169 ng/mL Standard Deviation 1255	—

Adverse Events

Posaconazole

Serious events: 178 serious events

Other events: 232 other events

Deaths: 99 deaths

Voriconazole

Serious events: 172 serious events

Other events: 225 other events

Deaths: 99 deaths

Serious adverse events

Measure	Posaconazole n=288 participants at risk Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 participants at risk Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Blood and lymphatic system disorders Anaemia	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Blood disorder	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Bone marrow failure	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Febrile neutropenia	8.3% 24/288 • Number of events 32 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	7.3% 21/287 • Number of events 26 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Leukopenia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Neutropenia	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Thrombocytopenia	0.35% 1/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Accessory cardiac pathway	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Acute coronary syndrome	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Acute left ventricular failure	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Angina pectoris	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Arrhythmia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Atrial fibrillation	1.4% 4/288 • Number of events 4 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Cardiac arrest	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Cardiac failure	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Cardiac failure acute	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Cardiac failure congestive	0.35% 1/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Left ventricular failure	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Myocardial infarction	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Ventricular extrasystoles	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Ventricular fibrillation	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Eye disorders Vision blurred	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Abdominal distension	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Abdominal pain	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Colitis	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Diarrhoea	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Duodenitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Gastric varices haemorrhage	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Gastritis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Gastrointestinal disorder	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Gastrointestinal hypomotility	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Ileus	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Inflammatory bowel disease	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Melaena	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Nausea	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Neutropenic colitis	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Pancreatitis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Stomatitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Vomiting	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Asthenia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Death	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders General physical health deterioration	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Hypothermia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Mucosal inflammation	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Multiple organ dysfunction syndrome	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Oedema	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Pain	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Pyrexia	2.4% 7/288 • Number of events 9 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.7% 5/287 • Number of events 5 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Cholangitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Cholecystitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Hepatic cirrhosis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Hepatic function abnormal	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Hepatocellular injury	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Hydrocholecystis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Hepatobiliary disorders Hyperbilirubinaemia	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Acute graft versus host disease	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Acute graft versus host disease in skin	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Engraftment syndrome	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Graft versus host disease in gastrointestinal tract	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Graft versus host disease in liver	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Haemophagocytic lymphohistiocytosis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Immune reconstitution inflammatory syndrome	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Immune system disorders Kidney transplant rejection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Abdominal abscess	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Abdominal sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Anal infection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Appendicitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Aspergillus infection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Atypical pneumonia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Bacteraemia	1.7% 5/288 • Number of events 5 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Bacterial pericarditis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Bacterial sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Brain abscess	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Bronchopulmonary aspergillosis	2.1% 6/288 • Number of events 6 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	2.1% 6/287 • Number of events 6 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Candida sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cellulitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cellulitis pharyngeal	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cerebral aspergillosis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Citrobacter sepsis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Clostridial infection	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Clostridium difficile colitis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Clostridium difficile infection	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Corona virus infection	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cystitis viral	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cytomegalovirus infection	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cytomegalovirus viraemia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Device related infection	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Device related sepsis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Disseminated cytomegaloviral infection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Diverticulitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Emphysematous cholecystitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Endocarditis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Endocarditis bacterial	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Enteritis infectious	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Enterobacter pneumonia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Enterobacter sepsis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Enterococcal bacteraemia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Enterococcal sepsis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Escherichia bacteraemia	1.0% 3/288 • Number of events 4 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Escherichia sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Febrile infection	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Fungal infection	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Gastroenteritis norovirus	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Hepatosplenic candidiasis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Herpes zoster	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Infection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Infectious pleural effusion	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Influenza	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Intervertebral discitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Klebsiella bacteraemia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Klebsiella sepsis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Lower respiratory tract infection bacterial	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Lower respiratory tract infection viral	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Meningitis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Mucormycosis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Muscle abscess	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Neutropenic sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Nocardiosis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Peritonitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumocystis jirovecii pneumonia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia	8.0% 23/288 • Number of events 27 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.2% 12/287 • Number of events 12 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia bacterial	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia cytomegaloviral	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia fungal	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia klebsiella	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia pseudomonal	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia viral	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pseudomembranous colitis	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pseudomonal bacteraemia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pseudomonal sepsis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pulmonary mycosis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pulmonary sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pulmonary tuberculosis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pyelonephritis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Relapsing fever	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Renal graft infection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Respiratory tract infection fungal	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Sepsis	3.5% 10/288 • Number of events 10 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	2.4% 7/287 • Number of events 7 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Sepsis syndrome	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Septic shock	5.6% 16/288 • Number of events 16 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.6% 16/287 • Number of events 16 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Sinusitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Sinusitis fungal	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Staphylococcal bacteraemia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Staphylococcal sepsis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Subcutaneous abscess	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Systemic candida	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Urinary tract infection	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Urinary tract infection enterococcal	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Varicella zoster virus infection	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Injury, poisoning and procedural complications Concussion	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Injury, poisoning and procedural complications Hip fracture	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Injury, poisoning and procedural complications Procedural pneumothorax	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Alanine aminotransferase increased	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Aspartate aminotransferase increased	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Blood alkaline phosphatase increased	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Blood creatinine increased	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Blood lactate dehydrogenase increased	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Cytomegalovirus test positive	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Gamma-glutamyltransferase increased	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Liver function test increased	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Neutrophil count decreased	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Transaminases increased	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Cachexia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Dehydration	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Diabetes mellitus	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hyperkalaemia	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hypokalaemia	1.4% 4/288 • Number of events 4 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Tumour lysis syndrome	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Musculoskeletal and connective tissue disorders Arthralgia	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Musculoskeletal and connective tissue disorders Back pain	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia recurrent	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	2.4% 7/288 • Number of events 7 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.2% 12/287 • Number of events 12 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia recurrent	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma recurrent	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell type acute leukaemia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blast crisis in myelogenous leukaemia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma refractory	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia recurrent	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphocytic leukaemia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour of the lung	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Precursor T-lymphoblastic lymphoma/leukaemia refractory	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Primary mediastinal large B-cell lymphoma	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Brain oedema	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Cerebral disorder	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Cerebral haemorrhage	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Cerebral infarction	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Cerebrovascular accident	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Dizziness	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Encephalopathy	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.7% 5/287 • Number of events 5 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Haemorrhage intracranial	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Headache	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Hypoaesthesia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Paraesthesia	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Seizure	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Status epilepticus	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Syncope	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Transient ischaemic attack	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Wernicke's encephalopathy	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Bipolar I disorder	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Confusional state	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Hallucination	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Mental status changes	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Suicide attempt	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Renal and urinary disorders Acute kidney injury	3.1% 9/288 • Number of events 9 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.7% 5/287 • Number of events 5 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Renal and urinary disorders Cystitis haemorrhagic	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Renal and urinary disorders Haematuria	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Aspiration	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.4% 4/288 • Number of events 4 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary cavitation	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.69% 2/288 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.70% 2/287 • Number of events 2 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.0% 3/287 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	1.4% 4/287 • Number of events 4 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.5% 10/288 • Number of events 10 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	2.4% 7/287 • Number of events 8 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Skin and subcutaneous tissue disorders Dermatitis exfoliative generalised	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/288 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Vascular disorders Aortic aneurysm	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Vascular disorders Deep vein thrombosis	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.35% 1/287 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Vascular disorders Hypotension	1.0% 3/288 • Number of events 3 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Vascular disorders Shock	0.35% 1/288 • Number of events 1 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	0.00% 0/287 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.

Other adverse events

Measure	Posaconazole n=288 participants at risk Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.	Voriconazole n=287 participants at risk Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
Blood and lymphatic system disorders Anaemia	8.0% 23/288 • Number of events 41 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	10.1% 29/287 • Number of events 46 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Febrile neutropenia	7.3% 21/288 • Number of events 24 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	6.3% 18/287 • Number of events 22 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Blood and lymphatic system disorders Thrombocytopenia	7.6% 22/288 • Number of events 28 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.9% 17/287 • Number of events 23 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Cardiac disorders Tachycardia	3.8% 11/288 • Number of events 14 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	6.3% 18/287 • Number of events 23 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Abdominal pain	9.4% 27/288 • Number of events 31 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.4% 24/287 • Number of events 24 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Constipation	11.1% 32/288 • Number of events 36 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.0% 23/287 • Number of events 26 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Diarrhoea	18.1% 52/288 • Number of events 66 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	17.4% 50/287 • Number of events 57 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Nausea	22.6% 65/288 • Number of events 83 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	17.4% 50/287 • Number of events 63 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Gastrointestinal disorders Vomiting	18.1% 52/288 • Number of events 64 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	13.2% 38/287 • Number of events 57 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Chest pain	6.2% 18/288 • Number of events 19 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	3.8% 11/287 • Number of events 11 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Chills	5.2% 15/288 • Number of events 19 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	2.8% 8/287 • Number of events 8 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Fatigue	6.6% 19/288 • Number of events 20 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	2.4% 7/287 • Number of events 8 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Oedema peripheral	11.1% 32/288 • Number of events 35 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.4% 24/287 • Number of events 27 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
General disorders Pyrexia	26.0% 75/288 • Number of events 122 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	24.0% 69/287 • Number of events 127 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Cytomegalovirus infection	5.2% 15/288 • Number of events 17 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.9% 14/287 • Number of events 16 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Infections and infestations Pneumonia	4.9% 14/288 • Number of events 14 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.2% 15/287 • Number of events 15 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Alanine aminotransferase increased	13.5% 39/288 • Number of events 49 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	11.8% 34/287 • Number of events 46 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Aspartate aminotransferase increased	12.5% 36/288 • Number of events 46 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	11.8% 34/287 • Number of events 41 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Blood alkaline phosphatase increased	7.3% 21/288 • Number of events 23 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	9.8% 28/287 • Number of events 33 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Blood bilirubin increased	8.3% 24/288 • Number of events 38 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	7.0% 20/287 • Number of events 24 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Blood lactate dehydrogenase increased	4.5% 13/288 • Number of events 17 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.9% 17/287 • Number of events 20 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Gamma-glutamyltransferase increased	4.5% 13/288 • Number of events 15 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.2% 15/287 • Number of events 21 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Investigations Platelet count decreased	5.2% 15/288 • Number of events 21 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	3.8% 11/287 • Number of events 18 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Decreased appetite	8.7% 25/288 • Number of events 25 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.9% 14/287 • Number of events 15 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hypocalcaemia	5.2% 15/288 • Number of events 25 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.5% 13/287 • Number of events 27 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hypokalaemia	27.1% 78/288 • Number of events 133 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	17.1% 49/287 • Number of events 72 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hypomagnesaemia	10.1% 29/288 • Number of events 48 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	6.3% 18/287 • Number of events 20 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hyponatraemia	4.2% 12/288 • Number of events 19 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	6.6% 19/287 • Number of events 26 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Metabolism and nutrition disorders Hypophosphataemia	7.6% 22/288 • Number of events 24 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	3.1% 9/287 • Number of events 11 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 17/288 • Number of events 21 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	3.1% 9/287 • Number of events 10 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Musculoskeletal and connective tissue disorders Pain in extremity	6.6% 19/288 • Number of events 20 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.5% 13/287 • Number of events 15 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Dizziness	7.3% 21/288 • Number of events 22 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	4.2% 12/287 • Number of events 12 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Nervous system disorders Headache	11.8% 34/288 • Number of events 45 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.4% 24/287 • Number of events 29 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Confusional state	2.8% 8/288 • Number of events 9 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.6% 16/287 • Number of events 16 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Psychiatric disorders Insomnia	6.2% 18/288 • Number of events 19 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.6% 16/287 • Number of events 17 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 30/288 • Number of events 32 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.4% 24/287 • Number of events 24 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.4% 27/288 • Number of events 28 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.4% 24/287 • Number of events 28 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.8% 31/288 • Number of events 34 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	5.9% 17/287 • Number of events 17 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Skin and subcutaneous tissue disorders Rash	6.6% 19/288 • Number of events 22 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	7.7% 22/287 • Number of events 32 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Vascular disorders Hypertension	9.7% 28/288 • Number of events 33 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	8.0% 23/287 • Number of events 25 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.
Vascular disorders Hypotension	5.9% 17/288 • Number of events 20 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.	6.6% 19/287 • Number of events 25 • Up to ~Week 16 (± 2 weeks) The analysis population was defined as all randomized participants who received at least one dose of study treatment. The analysis population for the all-cause mortality included all randomized participants.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media) that report any results of the trial.
• Publication restrictions are in place

Restriction type: OTHER