Trial Outcomes & Findings for Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (NCT NCT00104520)

Last Updated: 2011-03-11

Results Overview

The primary endpoint was time to need for a course of inhaled or IV antipseudomonal antibiotics with documented physician assessment of need for antibiotics. Antipseudomonal Antibiotic need was documented based on the presence of at least one of the following four symptoms predictive of pulmonary exacerbation: decreased exercise tolerance, increased cough, increased sputum / chest congestion, decreased appetite, or other.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

211 participants

Primary outcome timeframe

Day 0 to Day 84 (end of study)

Results posted on

2011-03-11

Participant Flow

Participants were enrolled at 56 sites in the United States. Date of first enrollment was 24 February 2005, and date of last participant follow-up was 07 September 2006.

Subjects were randomized in 1:1:2:2 ratio to placebo twice a day (BID) or three times a day (TID) and AZLI BID or TID, respectively. A total of 211 subjects were included in the ITT analyses: 38 placebo BID, 38 placebo TID, 69 AZLI BID, and 66 AZLI TID. All analyses were conducted on pooled placebo (n = 76) versus pooled AZLI (n = 135) groups.

Participant milestones

Participant milestones
Measure	Placebo (Pooled BID/TID) Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Overall Study STARTED	76	135
Overall Study COMPLETED	26	64
Overall Study NOT COMPLETED	50	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Pooled BID/TID) Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Overall Study Unrelated adverse event	34	47
Overall Study Study drug intolerance	0	1
Overall Study Related adverse event	13	15
Overall Study Lost to Follow-up	1	0
Overall Study Noncompliance	0	2
Overall Study Personal/administrative	1	1
Overall Study Other	1	5

Baseline Characteristics

Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Pooled BID/TID) n=76 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	Total n=211 Participants Total of all reporting groups
Age, Categorical <=18 years	12 Participants n=5 Participants	34 Participants n=7 Participants	46 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	63 Participants n=5 Participants	101 Participants n=7 Participants	164 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age Continuous	27.9 years STANDARD_DEVIATION 10.4 • n=5 Participants	25.3 years STANDARD_DEVIATION 10.2 • n=7 Participants	26.2 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	59 Participants n=7 Participants	90 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	76 Participants n=7 Participants	121 Participants n=5 Participants
Region of Enrollment United States	76 participants n=5 Participants	135 participants n=7 Participants	211 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 84 (end of study)

Population: Analysis based on intents to treat (ITT) population (all participants randomized to treatment who received at least part of one dose of study drug).

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=76 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics	71 Days Interval 57.0 to 97.0	92 Days Interval 89.0 to NA = not estimable

SECONDARY outcome

Timeframe: Day 0 to Day 28

Population: Analysis based on ITT population (all participants randomized to tx who received at least part of one dose of study drug). Missing baseline data were not imputed. Missing post-baseline data were imputed using worst-case value for participants who withdrew due to AE or study drug intolerance. For all other missing data, LOCF method was used.

The CFQ-R was administered at Day -28, baseline, Day 14, Day 28, and Day 84 (end of study). The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores \[units\]: 0-100; higher scores indicate fewer symptoms).

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=73 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=132 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score	-0.66 Units on a scale Standard Error 1.708	4.34 Units on a scale Standard Error 1.27

SECONDARY outcome

Timeframe: Day 0 to Day 28

Population: Analysis based on ITT population (all participants who received at least part of one dose of study drug). Missing baseline data were not imputed. Missing post-baseline data were imputed using worst-case value for participants who withdrew due to an AE or study drug intolerance. For all other missing data, LOCF imputation method was used.

Spirometry was performed at each visit. FEV1 was recorded according to American Thoracic Society (ATS) guidelines. FEV1(L) is the measurement of the volume of air (expressed in liters) exhaled in 1 second. The percent change in this parameter from Day 0 to Day 28 was determined for each treatment group.

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=76 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Percent Change in Forced Expiratory Volume in 1 Second (FEV1) (L)	-2.363 Percent change in FEV1 (L) Standard Error 1.534	3.917 Percent change in FEV1 (L) Standard Error 1.151

SECONDARY outcome

Timeframe: Day 0 to Day 84

Population: Analysis based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). No imputation methods were used for the analysis.

Details of all hospitalizations, including the dates of admission and discharge, were recorded on the electronic case report form (eCRF).

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=76 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Number of Hospitalization Days	0.5 Days Standard Deviation 2.4	0.9 Days Standard Deviation 3.9

SECONDARY outcome

Timeframe: Day 0 to Day 28

Population: Analysis based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). No imputation methods were used for the analysis.

Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=57 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=95 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum	0.225 Log10 PA CFUs/gram of sputum Standard Error 0.209	-0.434 Log10 PA CFUs/gram of sputum Standard Error 0.167

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 and Day 28

Population: Analysis based on ITT population (all participants who received at least part of one dose of study drug). No imputation methods were used for the analysis.

Sputum samples were collected at all visits for quantitative and qualitative culture for Staphylococcus aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. Number of participants with other pathogens at baseline and at the end of treatment (28 days) are reported.

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=76 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Number of Participants With Other Pathogens S. aureus - Day 28	23 Participants	63 Participants
Number of Participants With Other Pathogens A. xylosoxidans - Day 28	6 Participants	7 Participants
Number of Participants With Other Pathogens S. aureus - Day 0	23 Participants	58 Participants
Number of Participants With Other Pathogens B. cepacia - Day 0	0 Participants	0 Participants
Number of Participants With Other Pathogens B. cepacia - Day 28	0 Participants	0 Participants
Number of Participants With Other Pathogens S. maltophilia - Day 0	9 Participants	18 Participants
Number of Participants With Other Pathogens S. maltophilia - Day 28	8 Participants	19 Participants
Number of Participants With Other Pathogens A. xylosoxidans - Day 0	6 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 to Day 28

Population: Analysis based on ITT population (all participants who received at least part of one dose of study drug). No imputation methods were used for the analysis.

The aztreonam susceptibility of PA isolates from sputum samples (collected at all visits) was assessed. MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism). MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism). MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis.

Outcome measures

Outcome measures
Measure	Placebo (Pooled BID/TID) n=76 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Minimum Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Day 28 MIC90	64 μg/mL	64 μg/mL
Minimum Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Baseline MIC50	1 μg/mL	2 μg/mL
Minimum Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Day 28 MIC50	1 μg/mL	4 μg/mL
Minimum Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Baseline MIC90	64 μg/mL	32 μg/mL

Adverse Events

Placebo (Pooled BID/TID)

Serious events: 3 serious events

Other events: 65 other events

Deaths: 0 deaths

AZLI (Pooled BID/TID)

Serious events: 13 serious events

Other events: 121 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mark Bresnik, MD, Director, Clinical Research

Gilead Sciences, Inc.

Phone: (650) 522-5934

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution and investigator may publish or present the results of the trial generated there with prior written consent of Gilead; or 2 years after the trial has ended at all institutions. Proposed publications/target venue must go to Gilead 30 days (manuscripts) or 15 days (abstracts/presentations) prior. Any Gilead confidential information in the document(s) must be deleted, or if requested publication delayed for up to 45 days to permit Gilead to obtain intellectual property protection.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo (Pooled BID/TID) n=76 participants at risk Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 participants at risk AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Investigations Chest X-ray abnormal	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Chest discomfort	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Cough	1.3% 1/76 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	5.2% 7/135 • Number of events 7 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Crackles lung	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 2/76 • Number of events 2 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	1.5% 2/135 • Number of events 2 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
General disorders Exercise tolerance decreased	1.3% 1/76 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.00% 0/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
General disorders Fatigue	1.3% 1/76 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.00% 0/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Investigations Forced expiratory volume decreased	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Nervous system disorders Neurological symptoms	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Non-cardiac chest pain	1.3% 1/76 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Productive cough	2.6% 2/76 • Number of events 2 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	4.4% 6/135 • Number of events 6 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Investigations Pulmonary function test decreased	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	3.0% 4/135 • Number of events 4 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
General disorders Pyrexia	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	2.2% 3/135 • Number of events 3 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Injury, poisoning and procedural complications Spinal cord injury	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	0.74% 1/135 • Number of events 1 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	1.5% 2/135 • Number of events 2 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.

Other adverse events
Measure	Placebo (Pooled BID/TID) n=76 participants at risk Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered twice daily (BID) or three times daily (TID) by inhalation using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.	AZLI (Pooled BID/TID) n=135 participants at risk AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation BID or TID using the investigational nebulizer. All analyses were conducted on the pooled placebo vs pooled AZLI treatment groups.
Gastrointestinal disorders Abdominal pain	2.6% 2/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	7.4% 10/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Gastrointestinal disorders Abdominal pain upper	3.9% 3/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	5.2% 7/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Investigations Blood glucose increased	5.3% 4/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	1.5% 2/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Chest discomfort	7.9% 6/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	10.4% 14/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Cough	67.1% 51/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	60.0% 81/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Crackles lung	13.2% 10/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	8.1% 11/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Metabolism and nutrition disorders Decreased appetite	14.5% 11/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	8.1% 11/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Gastrointestinal disorders Diarrhoea	1.3% 1/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	5.9% 8/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.3% 4/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	1.5% 2/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 6/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	9.6% 13/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea exacerbated	7.9% 6/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	3.0% 4/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	6.6% 5/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	6.7% 9/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
General disorders Exercise tolerance decreased	13.2% 10/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	8.1% 11/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
General disorders Fatigue	15.8% 12/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	10.4% 14/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Forced expiratory volume decreased	5.3% 4/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	4.4% 6/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Haemoptysis	18.4% 14/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	12.6% 17/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Nervous system disorders Headache	11.8% 9/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	10.4% 14/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.5% 11/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	20.7% 28/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Gastrointestinal disorders Nausea	5.3% 4/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	3.0% 4/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	11.8% 9/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	13.3% 18/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Productive cough	35.5% 27/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	36.3% 49/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Investigations Pulmonary function test decreased	10.5% 8/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	6.7% 9/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
General disorders Pyrexia	2.6% 2/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	11.9% 16/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	19.7% 15/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	14.8% 20/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.9% 3/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	10.4% 14/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Sinus congestion	10.5% 8/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	5.9% 8/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Sinus headache	1.3% 1/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	5.2% 7/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Gastrointestinal disorders Vomiting	6.6% 5/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	6.7% 9/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Wheezing	11.8% 9/76 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.	16.3% 22/135 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose (Day 0 to Day 56) are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during treatment period of study, whether or not event was considered related to study participation or procedures. Participants were only counted once within an SOC and preferred term.