Trial Outcomes & Findings for Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis (NCT NCT01314716)

Last Updated: 2014-04-16

Results Overview

The mean (SD) change in the Respiratory Symptoms score on the Quality of Life Questionnaire-Bronchiectasis (QOL-B) was measured from baseline to the end of Course 1 (Day 28). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

274 participants

Primary outcome timeframe

Baseline to Day 28

Results posted on

2014-04-16

Participant Flow

Subjects were enrolled in a total of 90 study sites in the North America, Europe, and Australia. The first participant was screened on 25 April 2011. The last participant observation was on 01 July 2013.

404 participants were screened, 274 were randomized and comprise the Intent-to-Treat (ITT) Analysis Set. 272 randomized participants received at least one dose of study drug and comprise the Safety Analysis Set.

Participant milestones

Participant milestones
Measure	AZLI-AZLI Participants were randomized to receive blinded Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 84 days.	Placebo-AZLI Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 84 days.
Double-Blind Phase STARTED	136	138
Double-Blind Phase Randomized and Treated	135	137
Double-Blind Phase COMPLETED	119	123
Double-Blind Phase NOT COMPLETED	17	15
Open-Label Phase STARTED	112	110
Open-Label Phase COMPLETED	102	98
Open-Label Phase NOT COMPLETED	10	12

Reasons for withdrawal

Reasons for withdrawal
Measure	AZLI-AZLI Participants were randomized to receive blinded Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 84 days.	Placebo-AZLI Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 84 days.
Double-Blind Phase Randomized but not treated	1	1
Double-Blind Phase Adverse Event	10	4
Double-Blind Phase Withdrawal by Subject	5	6
Double-Blind Phase Lost to Follow-up	0	1
Double-Blind Phase Sponsor request	1	2
Double-Blind Phase Physician Decision	0	1
Open-Label Phase Adverse Event	4	6
Open-Label Phase Withdrawal by Subject	1	2
Open-Label Phase Physician Decision	5	4

Baseline Characteristics

Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZLI-AZLI n=136 Participants Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI n=138 Participants Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Total n=274 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 14.22 • n=93 Participants	62.7 years STANDARD_DEVIATION 13.33 • n=4 Participants	63.0 years STANDARD_DEVIATION 13.75 • n=27 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=93 Participants	66 Participants n=4 Participants	119 Participants n=27 Participants
Age, Categorical >=65 years	83 Participants n=93 Participants	72 Participants n=4 Participants	155 Participants n=27 Participants
Sex: Female, Male Female	89 Participants n=93 Participants	101 Participants n=4 Participants	190 Participants n=27 Participants
Sex: Female, Male Male	47 Participants n=93 Participants	37 Participants n=4 Participants	84 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	122 Participants n=93 Participants	112 Participants n=4 Participants	234 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=93 Participants	19 Participants n=4 Participants	28 Participants n=27 Participants
Race/Ethnicity, Customized White	119 participants n=93 Participants	128 participants n=4 Participants	247 participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Race/Ethnicity, Customized Asian	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized Black or African Heritage	2 participants n=93 Participants	4 participants n=4 Participants	6 participants n=27 Participants
Race/Ethnicity, Customized Other	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Race/Ethnicity, Customized Not permitted	11 participants n=93 Participants	4 participants n=4 Participants	15 participants n=27 Participants
Region of Enrollment France	11 participants n=93 Participants	3 participants n=4 Participants	14 participants n=27 Participants
Region of Enrollment United States	58 participants n=93 Participants	52 participants n=4 Participants	110 participants n=27 Participants
Region of Enrollment Canada	0 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Spain	22 participants n=93 Participants	17 participants n=4 Participants	39 participants n=27 Participants
Region of Enrollment Belgium	5 participants n=93 Participants	6 participants n=4 Participants	11 participants n=27 Participants
Region of Enrollment Australia	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Netherlands	5 participants n=93 Participants	12 participants n=4 Participants	17 participants n=27 Participants
Region of Enrollment Germany	16 participants n=93 Participants	21 participants n=4 Participants	37 participants n=27 Participants
Region of Enrollment United Kingdom	11 participants n=93 Participants	11 participants n=4 Participants	22 participants n=27 Participants
Region of Enrollment Italy	5 participants n=93 Participants	12 participants n=4 Participants	17 participants n=27 Participants
QOL-B Respiratory Symptom Score	56.2 units on a scale STANDARD_DEVIATION 17.98 • n=93 Participants	57.4 units on a scale STANDARD_DEVIATION 18.07 • n=4 Participants	56.8 units on a scale STANDARD_DEVIATION 18.00 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Day 28

Population: Participants in the ITT Analysis Set with scores at both baseline and Day 28 were analyzed.

Outcome measures

Outcome measures
Measure	AZLI-AZLI n=128 Participants Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI n=132 Participants Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
Change in QOL-B Respiratory Symptoms Score at Day 28	8.2 units on a scale Standard Deviation 17.13	3.2 units on a scale Standard Deviation 14.67

SECONDARY outcome

Timeframe: Baseline to Day 84

Population: Participants in the ITT Analysis Set with scores at both baseline and Day 84 were analyzed.

The mean (SD) change in the Respiratory Symptoms score on the QOL-B was measured from baseline to the end of Course 2 (Day 84). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Outcome measures

Outcome measures
Measure	AZLI-AZLI n=123 Participants Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI n=125 Participants Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
Change in QOL-B Respiratory Symptoms Score at Day 84	5.6 units on a scale Standard Deviation 16.44	3.9 units on a scale Standard Deviation 17.73

SECONDARY outcome

Timeframe: Baseline to Day 112

Population: ITT Analysis Set

Protocol-defined exacerbation was defined as an acute worsening of respiratory disease that triggered the initiation of a non-study antibiotic meeting at least 3 major criteria, or 2 major and at least 2 minor criteria. * Major Criteria: increased sputum production; increased discoloration of sputum; increased dyspnea; increased cough * Minor Criteria: fever (\> 38º C) measured during clinic visit; increased malaise or fatigue; forced expiratory volume in 1 second (FEV1) (L) or forced vital capacity (FVC) decreased \> 10% from baseline; new or increased hemoptysis

Outcome measures

Outcome measures
Measure	AZLI-AZLI n=136 Participants Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI n=138 Participants Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
Time to Protocol-Defined Exacerbation (PDE)	NA days At least 50% of participants must have had a PDE in order to compute the median days to PDE. Fewer than 50% of participants in this group had a PDE, so median days to PDE could not be computed.	NA days At least 50% of participants must have had a PDE in order to compute the median days to PDE. Fewer than 50% of participants in this group had a PDE, so median days to PDE could not be computed.

Adverse Events

AZLI-AZLI (Double-Blind)

Serious events: 18 serious events

Other events: 112 other events

Deaths: 0 deaths

Placebo-AZLI (Double-Blind)

Serious events: 16 serious events

Other events: 101 other events

Deaths: 0 deaths

AZLI-AZLI (Open-Label)

Serious events: 8 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo-AZLI (Open-Label)

Serious events: 9 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	AZLI-AZLI (Double-Blind) n=135 participants at risk Adverse events for this reporting group were reported from baseline to Day 112 while participants were receiving double-blind AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI (Double-Blind) n=137 participants at risk Adverse events for this reporting group were reported from baseline to Day 112 while participants were receiving double-blind placebo; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	AZLI-AZLI (Open-Label) n=112 participants at risk Adverse events for this reporting group were reported from Day 112 to Day 196 plus 30 days while participants were receiving open-label AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI (Open-Label) n=110 participants at risk Adverse events for this reporting group were reported from Day 112 to Day 196 plus 30 days while participants were receiving open-label AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
Infections and infestations Infective exacerbation of bronchiectasis	3.0% 4/135 • Baseline up to 30 days after the last dose of study drug	1.5% 2/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	2.7% 3/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Pneumonia	2.2% 3/135 • Baseline up to 30 days after the last dose of study drug	1.5% 2/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Bronchitis	1.5% 2/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Diverticulitis	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Mycobacterium avium complex infection	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Fungal oesophagitis	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Lung infection pseudomonal	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Sinusitis	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.5% 2/135 • Baseline up to 30 days after the last dose of study drug	4.4% 6/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Asthma	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Lung disorder	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	1.8% 2/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Ankle fracture	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Hip fracture	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Patella fracture	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Fall	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Musculoskeletal and connective tissue disorders Arthralgia	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Cardiac disorders Cardiac failure	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Cardiac disorders Atrial fibrillation	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Gastrointestinal disorders Abdominal pain upper	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Gastrointestinal disorders Intestinal obstruction	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Endocrine disorders Hyperthyroidism	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.73% 1/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Vascular disorders Hypertensive crisis	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Lung infection	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Gastroenteritis	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	1.8% 2/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Femur fracture	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Injury, poisoning and procedural complications Foot fracture	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug
Renal and urinary disorders Renal failure acute	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug
General disorders Device malfunction	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.89% 1/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Psychiatric disorders Depression	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.91% 1/110 • Baseline up to 30 days after the last dose of study drug

Measure	AZLI-AZLI (Double-Blind) n=135 participants at risk Adverse events for this reporting group were reported from baseline to Day 112 while participants were receiving double-blind AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI (Double-Blind) n=137 participants at risk Adverse events for this reporting group were reported from baseline to Day 112 while participants were receiving double-blind placebo; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	AZLI-AZLI (Open-Label) n=112 participants at risk Adverse events for this reporting group were reported from Day 112 to Day 196 plus 30 days while participants were receiving open-label AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	Placebo-AZLI (Open-Label) n=110 participants at risk Adverse events for this reporting group were reported from Day 112 to Day 196 plus 30 days while participants were receiving open-label AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
Respiratory, thoracic and mediastinal disorders Sputum discoloured	35.6% 48/135 • Baseline up to 30 days after the last dose of study drug	27.7% 38/137 • Baseline up to 30 days after the last dose of study drug	18.8% 21/112 • Baseline up to 30 days after the last dose of study drug	16.4% 18/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Cough	48.9% 66/135 • Baseline up to 30 days after the last dose of study drug	47.4% 65/137 • Baseline up to 30 days after the last dose of study drug	24.1% 27/112 • Baseline up to 30 days after the last dose of study drug	34.5% 38/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Sputum increased	43.7% 59/135 • Baseline up to 30 days after the last dose of study drug	36.5% 50/137 • Baseline up to 30 days after the last dose of study drug	17.0% 19/112 • Baseline up to 30 days after the last dose of study drug	20.9% 23/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Dyspnoea	37.0% 50/135 • Baseline up to 30 days after the last dose of study drug	34.3% 47/137 • Baseline up to 30 days after the last dose of study drug	23.2% 26/112 • Baseline up to 30 days after the last dose of study drug	25.5% 28/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Wheezing	13.3% 18/135 • Baseline up to 30 days after the last dose of study drug	9.5% 13/137 • Baseline up to 30 days after the last dose of study drug	9.8% 11/112 • Baseline up to 30 days after the last dose of study drug	6.4% 7/110 • Baseline up to 30 days after the last dose of study drug
General disorders Fatigue	18.5% 25/135 • Baseline up to 30 days after the last dose of study drug	18.2% 25/137 • Baseline up to 30 days after the last dose of study drug	12.5% 14/112 • Baseline up to 30 days after the last dose of study drug	14.5% 16/110 • Baseline up to 30 days after the last dose of study drug
General disorders Malaise	10.4% 14/135 • Baseline up to 30 days after the last dose of study drug	13.9% 19/137 • Baseline up to 30 days after the last dose of study drug	3.6% 4/112 • Baseline up to 30 days after the last dose of study drug	5.5% 6/110 • Baseline up to 30 days after the last dose of study drug
General disorders Pyrexia	22.2% 30/135 • Baseline up to 30 days after the last dose of study drug	15.3% 21/137 • Baseline up to 30 days after the last dose of study drug	10.7% 12/112 • Baseline up to 30 days after the last dose of study drug	14.5% 16/110 • Baseline up to 30 days after the last dose of study drug
General disorders Non-cardiac chest pain	6.7% 9/135 • Baseline up to 30 days after the last dose of study drug	9.5% 13/137 • Baseline up to 30 days after the last dose of study drug	4.5% 5/112 • Baseline up to 30 days after the last dose of study drug	9.1% 10/110 • Baseline up to 30 days after the last dose of study drug
Nervous system disorders Headache	12.6% 17/135 • Baseline up to 30 days after the last dose of study drug	10.2% 14/137 • Baseline up to 30 days after the last dose of study drug	6.2% 7/112 • Baseline up to 30 days after the last dose of study drug	10.0% 11/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Haemoptysis	8.9% 12/135 • Baseline up to 30 days after the last dose of study drug	8.0% 11/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Productive cough	5.2% 7/135 • Baseline up to 30 days after the last dose of study drug	2.9% 4/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.9% 12/135 • Baseline up to 30 days after the last dose of study drug	10.2% 14/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Respiratory, thoracic and mediastinal disorders Throat irritation	5.2% 7/135 • Baseline up to 30 days after the last dose of study drug	2.9% 4/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
General disorders Chills	7.4% 10/135 • Baseline up to 30 days after the last dose of study drug	2.2% 3/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Gastrointestinal disorders Diarrhoea	4.4% 6/135 • Baseline up to 30 days after the last dose of study drug	5.8% 8/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Gastrointestinal disorders Nausea	5.2% 7/135 • Baseline up to 30 days after the last dose of study drug	3.6% 5/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Musculoskeletal and connective tissue disorders Arthralgia	4.4% 6/135 • Baseline up to 30 days after the last dose of study drug	7.3% 10/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Infections and infestations Rhinitis	1.5% 2/135 • Baseline up to 30 days after the last dose of study drug	5.1% 7/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
Psychiatric disorders Insomnia	0.74% 1/135 • Baseline up to 30 days after the last dose of study drug	5.1% 7/137 • Baseline up to 30 days after the last dose of study drug	0.00% 0/112 • Baseline up to 30 days after the last dose of study drug	0.00% 0/110 • Baseline up to 30 days after the last dose of study drug
General disorders Pain	0.00% 0/135 • Baseline up to 30 days after the last dose of study drug	0.00% 0/137 • Baseline up to 30 days after the last dose of study drug	6.2% 7/112 • Baseline up to 30 days after the last dose of study drug	2.7% 3/110 • Baseline up to 30 days after the last dose of study drug