Trial Outcomes & Findings for Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis (NCT NCT01313624)

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

266 participants

Primary outcome timeframe

Baseline to Day 28

Results posted on

2014-04-16

Participant Flow

Subjects were enrolled in a total of 57 study sites in the United States, Canada, and Australia. The first participant was screened on 25 April 2011. The last participant observation was on 04 June 2013.

348 participants were screened and 266 were randomized and treated, and comprise the Safety Analysis Set and the Intent-to-Treat (ITT) 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 28 days plus 56 days of treatment-free follow-up.	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 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.
Double-Blind Phase STARTED	134	132
Double-Blind Phase COMPLETED	96	122
Double-Blind Phase NOT COMPLETED	38	10
Open-Label Phase STARTED	96	122
Open-Label Phase COMPLETED	92	109
Open-Label Phase NOT COMPLETED	4	13

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 28 days plus 56 days of treatment-free follow-up.	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 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.
Double-Blind Phase Adverse Event	27	4
Double-Blind Phase Withdrawal by Subject	9	4
Double-Blind Phase Lost to Follow-up	0	2
Double-Blind Phase Physician Decision	1	0
Double-Blind Phase Lack of Efficacy	1	0
Open-Label Phase Adverse Event	1	10
Open-Label Phase Withdrawal by Subject	2	2
Open-Label Phase Lost to Follow-up	1	1

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=134 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 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.	Total n=266 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 12.92 • n=5 Participants	64.9 years STANDARD_DEVIATION 12.11 • n=7 Participants	64.6 years STANDARD_DEVIATION 12.51 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=5 Participants	54 Participants n=7 Participants	107 Participants n=5 Participants
Age, Categorical >=65 years	81 Participants n=5 Participants	78 Participants n=7 Participants	159 Participants n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	97 Participants n=7 Participants	181 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	35 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=5 Participants	121 Participants n=7 Participants	242 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	121 participants n=5 Participants	119 participants n=7 Participants	240 participants n=5 Participants
Race/Ethnicity, Customized African-American	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Not Permitted	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	86 participants n=5 Participants	79 participants n=7 Participants	165 participants n=5 Participants
Region of Enrollment Canada	17 participants n=5 Participants	11 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Australia	31 participants n=5 Participants	42 participants n=7 Participants	73 participants n=5 Participants
QOL-B Respiratory Symptom Score	55.0 units on a scale STANDARD_DEVIATION 19.32 • n=5 Participants	55.5 units on a scale STANDARD_DEVIATION 19.26 • n=7 Participants	55.2 units on a scale STANDARD_DEVIATION 19.26 • n=5 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=117 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=124 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	7.4 units on a scale Standard Deviation 21.37	5.7 units on a scale Standard Deviation 13.62

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=108 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=122 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	7.4 units on a scale Standard Deviation 21.67	4.7 units on a scale Standard Deviation 17.24

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=134 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.
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.	120 days Interval 117.0 to The 95% upper confidence interval (CI) could not be estimated due to an insufficient number of PDE events.

Adverse Events

AZLI-AZLI (Double-Blind)

Serious events: 28 serious events

Other events: 116 other events

Deaths: 0 deaths

Placebo-AZLI (Double-Blind)

Serious events: 13 serious events

Other events: 102 other events

Deaths: 0 deaths

AZLI-AZLI (Open-Label)

Serious events: 9 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo-AZLI (Open-Label)

Serious events: 18 serious events

Other events: 76 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=134 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 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 (Double-Blind) n=132 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 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.	AZLI-AZLI (Open-Label) n=96 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 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 (Open-Label) n=122 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 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.
Infections and infestations Infective exacerbation of bronchiectasis	3.7% 5/134 • Baseline up to 30 days after the last dose of study drug.	3.0% 4/132 • Baseline up to 30 days after the last dose of study drug.	5.2% 5/96 • Baseline up to 30 days after the last dose of study drug.	5.7% 7/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Pneumonia	3.7% 5/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	2.1% 2/96 • Baseline up to 30 days after the last dose of study drug.	4.9% 6/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Bronchitis	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Bronchopneumonia	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Lung infection pseudomonal	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Infected skin ulcer	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Sinusitis	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Urinary tract infection	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.2% 3/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm	2.2% 3/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	1.0% 1/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 2/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 2/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Sputum increased	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	1.0% 1/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
Cardiac disorders Atrial fibrillation	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	1.6% 2/122 • Baseline up to 30 days after the last dose of study drug.
Cardiac disorders Tachycardia	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
Cardiac disorders Cardiac arrest	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Orthostatic intolerance	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Haemorrhage intracranial	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Memory impairment	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Cognitive disorder	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Dizziness	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Transient ischaemic attack	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Pyrexia	1.5% 2/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Gait disturbance	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Immune system disorders Hypersensitivity	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Immune system disorders Drug hypersensitivity	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Metabolism and nutrition disorders Dehydration	1.5% 2/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Investigations Electrocardiogram abnormal	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.76% 1/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis	0.75% 1/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Infections and infestations Acute sinusitis	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	1.0% 1/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Cardiac disorders Coronary artery disease	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	1.0% 1/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Systemic inflammatory response syndrome	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	1.0% 1/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Non-cardiac chest pain	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
Renal and urinary disorders Renal failure acute	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	1.6% 2/122 • Baseline up to 30 days after the last dose of study drug.
Immune system disorders Type IV hypersensitivity reaction	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/134 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.82% 1/122 • Baseline up to 30 days after the last dose of study drug.

Measure	AZLI-AZLI (Double-Blind) n=134 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 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 (Double-Blind) n=132 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 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.	AZLI-AZLI (Open-Label) n=96 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 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 (Open-Label) n=122 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 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.
Respiratory, thoracic and mediastinal disorders Cough	51.5% 69/134 • Baseline up to 30 days after the last dose of study drug.	43.2% 57/132 • Baseline up to 30 days after the last dose of study drug.	36.5% 35/96 • Baseline up to 30 days after the last dose of study drug.	41.0% 50/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Sputum Increased	46.3% 62/134 • Baseline up to 30 days after the last dose of study drug.	36.4% 48/132 • Baseline up to 30 days after the last dose of study drug.	30.2% 29/96 • Baseline up to 30 days after the last dose of study drug.	29.5% 36/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Sputum discoloured	31.3% 42/134 • Baseline up to 30 days after the last dose of study drug.	25.0% 33/132 • Baseline up to 30 days after the last dose of study drug.	25.0% 24/96 • Baseline up to 30 days after the last dose of study drug.	21.3% 26/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.0% 8/134 • Baseline up to 30 days after the last dose of study drug.	9.1% 12/132 • Baseline up to 30 days after the last dose of study drug.	5.2% 5/96 • Baseline up to 30 days after the last dose of study drug.	7.4% 9/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	54.5% 73/134 • Baseline up to 30 days after the last dose of study drug.	35.6% 47/132 • Baseline up to 30 days after the last dose of study drug.	32.3% 31/96 • Baseline up to 30 days after the last dose of study drug.	38.5% 47/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.4% 14/134 • Baseline up to 30 days after the last dose of study drug.	12.9% 17/132 • Baseline up to 30 days after the last dose of study drug.	4.2% 4/96 • Baseline up to 30 days after the last dose of study drug.	5.7% 7/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.5% 6/134 • Baseline up to 30 days after the last dose of study drug.	5.3% 7/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.0% 4/134 • Baseline up to 30 days after the last dose of study drug.	5.3% 7/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	15.7% 21/134 • Baseline up to 30 days after the last dose of study drug.	10.6% 14/132 • Baseline up to 30 days after the last dose of study drug.	6.2% 6/96 • Baseline up to 30 days after the last dose of study drug.	10.7% 13/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.5% 10/134 • Baseline up to 30 days after the last dose of study drug.	5.3% 7/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	10.4% 14/134 • Baseline up to 30 days after the last dose of study drug.	2.3% 3/132 • Baseline up to 30 days after the last dose of study drug.	6.2% 6/96 • Baseline up to 30 days after the last dose of study drug.	4.1% 5/122 • Baseline up to 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.2% 7/134 • Baseline up to 30 days after the last dose of study drug.	5.3% 7/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Fatigue	41.8% 56/134 • Baseline up to 30 days after the last dose of study drug.	22.0% 29/132 • Baseline up to 30 days after the last dose of study drug.	22.9% 22/96 • Baseline up to 30 days after the last dose of study drug.	15.6% 19/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Malaise	8.2% 11/134 • Baseline up to 30 days after the last dose of study drug.	10.6% 14/132 • Baseline up to 30 days after the last dose of study drug.	5.2% 5/96 • Baseline up to 30 days after the last dose of study drug.	4.1% 5/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Pyrexia	23.9% 32/134 • Baseline up to 30 days after the last dose of study drug.	12.1% 16/132 • Baseline up to 30 days after the last dose of study drug.	7.3% 7/96 • Baseline up to 30 days after the last dose of study drug.	9.8% 12/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Non-cardiac chest pain	14.9% 20/134 • Baseline up to 30 days after the last dose of study drug.	10.6% 14/132 • Baseline up to 30 days after the last dose of study drug.	6.2% 6/96 • Baseline up to 30 days after the last dose of study drug.	6.6% 8/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Chills	13.4% 18/134 • Baseline up to 30 days after the last dose of study drug.	4.5% 6/132 • Baseline up to 30 days after the last dose of study drug.	6.2% 6/96 • Baseline up to 30 days after the last dose of study drug.	2.5% 3/122 • Baseline up to 30 days after the last dose of study drug.
General disorders Oedema peripheral	5.2% 7/134 • Baseline up to 30 days after the last dose of study drug.	4.5% 6/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Headache	15.7% 21/134 • Baseline up to 30 days after the last dose of study drug.	17.4% 23/132 • Baseline up to 30 days after the last dose of study drug.	5.2% 5/96 • Baseline up to 30 days after the last dose of study drug.	5.7% 7/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Sinus headache	6.0% 8/134 • Baseline up to 30 days after the last dose of study drug.	1.5% 2/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Nervous system disorders Dizziness	7.5% 10/134 • Baseline up to 30 days after the last dose of study drug.	4.5% 6/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Gastrointestinal disorders Nausea	9.7% 13/134 • Baseline up to 30 days after the last dose of study drug.	8.3% 11/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Gastrointestinal disorders Vomiting	5.2% 7/134 • Baseline up to 30 days after the last dose of study drug.	4.5% 6/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Gastrointestinal disorders Diarrhoea	7.5% 10/134 • Baseline up to 30 days after the last dose of study drug.	9.1% 12/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.
Metabolism and nutrition disorders Decreased appetite	6.0% 8/134 • Baseline up to 30 days after the last dose of study drug.	3.8% 5/132 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/96 • Baseline up to 30 days after the last dose of study drug.	0.00% 0/122 • Baseline up to 30 days after the last dose of study drug.