Trial Outcomes & Findings for Assessing the Safety and Efficacy of MK-5592 (Posaconazole) in Japanese Participants With Fungal Infection (MK-5592-101) (NCT NCT02180165)

Last Updated: 2021-01-28

Results Overview

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

116 participants

Primary outcome timeframe

Up to approximately Day 98

Results posted on

2021-01-28

Participant Flow

This study was conducted in male and female Japanese participants with deep-seated fungal infection.

Participant milestones

Participant milestones
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis or with fusariosis or zygomycosis, received 300 mg posaconazole oral tablet (or 300 mg intravenous \[IV\] solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole Participants with aspergillosis or with fusariosis or zygomycosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole Participants with aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Overall Study COMPLETED	4	6	34	25
Overall Study NOT COMPLETED	11	1	29	6
Overall Study STARTED	15	7	63	31
Overall Study Treated Participants	15	7	62	31
Overall Study Type of Aspergillosis	15	7	57	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis or with fusariosis or zygomycosis, received 300 mg posaconazole oral tablet (or 300 mg intravenous \[IV\] solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole Participants with aspergillosis or with fusariosis or zygomycosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole Participants with aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Overall Study Not Treated	0	0	1	0
Overall Study Adverse Event	7	0	18	3
Overall Study Lack of Efficacy	0	1	3	2
Overall Study Physician Decision	1	0	5	0
Overall Study Withdrawal by Subject	3	0	2	1

Baseline Characteristics

Assessing the Safety and Efficacy of MK-5592 (Posaconazole) in Japanese Participants With Fungal Infection (MK-5592-101)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Posaconazole n=15 Participants Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg intravenous (IV) solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole n=7 Participants Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=57 Participants Participants from cohort 2 with invasive aspergillosis and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=27 Participants Participants from cohort 2 with invasive aspergillosis and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Total n=106 Participants Total of all reporting groups
Age, Continuous	64.3 Years STANDARD_DEVIATION 9.5 • n=5 Participants	69.9 Years STANDARD_DEVIATION 4.5 • n=7 Participants	65.6 Years STANDARD_DEVIATION 12.3 • n=5 Participants	58.2 Years STANDARD_DEVIATION 13.9 • n=4 Participants	63.8 Years STANDARD_DEVIATION 12.4 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	4 Participants n=7 Participants	54 Participants n=5 Participants	25 Participants n=4 Participants	95 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants	7 Participants n=7 Participants	57 Participants n=5 Participants	27 Participants n=4 Participants	106 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to approximately Day 98

Population: Cohort 1: All randomized participants with chronic pulmonary aspergillosis who received at least one dose of study treatment. Cohort 2: All randomized participants with invasive aspergillosis and chronic pulmonary aspergillosis who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole n=15 Participants Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole n=7 Participants Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=57 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=27 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Number of Participants With an Adverse Event	15 Participants	6 Participants	57 Participants	27 Participants

SECONDARY outcome

Timeframe: Day 42

Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.

Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by the clinical adjudication committee (CAC). The 95% confidence interval (CI) is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42	—	—	40.0 Percentage of participants Interval 5.3 to 85.3	100 Percentage of participants Interval 29.2 to 100.0

SECONDARY outcome

Timeframe: Day 84

Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84	—	—	60.0 Percentage of participants Interval 14.7 to 94.7	100 Percentage of participants Interval 29.2 to 100.0

SECONDARY outcome

Timeframe: Day 42

Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.

Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42	—	—	56.3 Percentage of participants Interval 41.2 to 70.5	87.0 Percentage of participants Interval 66.4 to 97.2

SECONDARY outcome

Timeframe: Day 84

Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84	—	—	58.3 Percentage of participants Interval 43.2 to 72.4	87.0 Percentage of participants Interval 66.4 to 97.2

SECONDARY outcome

Timeframe: Day 84

Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis or chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.

Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by CAC. Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment.The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=53 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=26 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84)	—	—	58.5 Percentage of participants Interval 44.1 to 71.9	88.5 Percentage of participants Interval 69.8 to 97.6

SECONDARY outcome

Timeframe: Day 42

Population: Participants in cohort 2, posaconazole treatment only, diagnosed by CAC with proven or probable zygomycosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1, and cohort 2 voriconazole treatment were not analyzed for this outcome measure.

Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 42	—	—	66.7 Percentage of participants	—

SECONDARY outcome

Timeframe: Day 84

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 84	—	—	100 Percentage of participants	—

SECONDARY outcome

Timeframe: Day 42

Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator	—	—	80.0 Percentage of participants Interval 28.4 to 99.5	66.7 Percentage of participants Interval 9.4 to 99.2

SECONDARY outcome

Timeframe: Day 84

Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator	—	—	60.4 Percentage of participants Interval 45.3 to 74.2	78.3 Percentage of participants Interval 56.3 to 92.5

SECONDARY outcome

Timeframe: Day 42

A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 Resolution	—	—	60.0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 Improvement	—	—	20.0 Percentage of participants	66.7 Percentage of participants

SECONDARY outcome

Timeframe: Day 84

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 Resolution	—	—	60.0 Percentage of participants	33.3 Percentage of participants
Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 Improvement	—	—	20.0 Percentage of participants	33.3 Percentage of participants

SECONDARY outcome

Timeframe: Day 42

A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 Resolution	—	—	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 Improvement	—	—	40.0 Percentage of participants	100 Percentage of participants

SECONDARY outcome

Timeframe: Day 84

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 Resolution	—	—	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 Improvement	—	—	60.0 Percentage of participants	100 Percentage of participants

SECONDARY outcome

Timeframe: Day 42

A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=5 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=3 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42	—	—	20.0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 42

A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42	—	—	43.8 Percentage of participants	73.9 Percentage of participants

SECONDARY outcome

Timeframe: Day 84

A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84	—	—	45.8 Percentage of participants	82.6 Percentage of participants

SECONDARY outcome

Timeframe: Day 42

A radiological response of resolution is defined as resolution of radiological lesions, as assessed by the CAC.

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42	—	—	58.3 Percentage of participants	87.0 Percentage of participants

SECONDARY outcome

Timeframe: Day 42

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42	—	—	33.3 Percentage of participants	21.7 Percentage of participants

SECONDARY outcome

Timeframe: Day 84

Outcome measures

Outcome measures
Measure	Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=48 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 2: Voriconazole n=23 Participants Participants from cohort 2 with invasive and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84	—	—	35.4 Percentage of participants	21.7 Percentage of participants

Adverse Events

Cohort 1: Posaconazole

Serious events: 3 serious events

Other events: 15 other events

Deaths: 1 deaths

Cohort 1: Voriconazole

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Cohort 2: Posaconazole

Serious events: 28 serious events

Other events: 58 other events

Deaths: 6 deaths

Cohort 2: Voriconazole

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort 1: Posaconazole n=15 participants at risk Participants with chronic pulmonary aspergillosis or with fusariosis or zygomycosis, received 300 mg posaconazole oral tablet (or 300 mg intravenous (IV) solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days	Cohort 1: Voriconazole n=7 participants at risk Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days	Cohort 2: Posaconazole n=62 participants at risk Participants with aspergillosis or with fusariosis or zygomycosis,received 300 mg posaconazole oral tablet (or 300 mg intravenous (IV) solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days. Participants with fusariosis or zygomycosis, were also assigned to this treatment group	Cohort 2: Voriconazole n=31 participants at risk Participants with aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure congestive	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Cardiac disorders Cor pulmonale	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
General disorders Chest pain	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
General disorders Malaise	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
General disorders Multiple organ dysfunction syndrome	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
General disorders Pyrexia	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 2/62 • Number of events 2 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 1/31 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Blister infected	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/62 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 1/31 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Bronchopulmonary aspergillosis	6.7% 1/15 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/62 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/62 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 1/31 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Osteomyelitis	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	13.3% 2/15 • Number of events 2 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	11.3% 7/62 • Number of events 7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Pneumonia bacterial	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 2/62 • Number of events 2 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Pyelonephritis	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Sepsis	6.7% 1/15 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/62 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Investigations Neutrophil count decreased	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Investigations White blood cell count decreased	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 2 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 1/31 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/62 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 1/31 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Nervous system disorders Loss of consciousness	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 2/62 • Number of events 2 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 1/31 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	3.2% 2/62 • Number of events 2 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/15 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/7 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	1.6% 1/62 • Number of events 1 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.	0.00% 0/31 • Up to approximately Day 98 All randomized participants who received at least one dose of study treatment.