Trial Outcomes & Findings for Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (NCT NCT00712166)

Last Updated: 2010-12-20

Results Overview

The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

160 participants

Primary outcome timeframe

Day 0 to Day 28

Results posted on

2010-12-20

Participant Flow

Participants were randomized at 39 sites in total: 34 in the United States, 1 in Canada, and 4 in Australia. Date of first screening was 16 June 2008, and date of last participant observation was 19 June 2009.

Planned trial size was approximately 140 participants randomized in 1:1 ratio to aztreonam for inhalation solution (AZLI) three times daily (TID) or placebo TID. 160 participants were randomized, 157 received blinded study drug (76 AZLI; 81 placebo). One participant who was randomized and treated with study drug discontinued the study.

Participant milestones

Participant milestones
Measure	Placebo Three Times Daily (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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (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 TID using the investigational nebulizer.
Overall Study STARTED	81	76
Overall Study COMPLETED	81	75
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Three Times Daily (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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (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 TID using the investigational nebulizer.
Overall Study Noncompliance	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.	Total n=157 Participants Total of all reporting groups
Age, Categorical <=18 years	47 Participants n=5 Participants	42 Participants n=7 Participants	89 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	18.9 years STANDARD_DEVIATION 9.11 • n=5 Participants	19.5 years STANDARD_DEVIATION 9.07 • n=7 Participants	19.2 years STANDARD_DEVIATION 9.07 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	30 Participants n=7 Participants	67 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	46 Participants n=7 Participants	90 Participants n=5 Participants
Region of Enrollment United States	73 participants n=5 Participants	72 participants n=7 Participants	145 participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Australia	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 28

Population: Analysis on intent-to-treat (ITT) population (received at least part of 1 dose of AZLI/placebo). Missing baseline data not imputed. Missing post-baseline data imputed with worst-case value for participants who withdrew due to an adverse event (AE)/study drug intolerance. Imputation for other missing data was last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28	1.41 Units on a scale Standard Error 1.64	3.22 Units on a scale Standard Error 1.71

SECONDARY outcome

Timeframe: Day 0 to Day 14

Population: Analysis based on ITT population (all participants receiving at least part of one dose of AZLI or placebo). 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.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Change From Baseline in CFQ-R RSS Score at Day 14	0.28 Units on a scale Standard Error 1.56	3.65 Units on a scale Standard Error 1.63

SECONDARY outcome

Timeframe: Day 0 to Day 42

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Change From Baseline in CFQ-R RSS Score at Day 42	2.91 Units on a scale Standard Error 1.65	3.02 Units on a scale Standard Error 1.72

SECONDARY outcome

Timeframe: Day 0 to Day 28

The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0 (baseline), 14, 28, and 42 (the last study visit). The endpoint was change from baseline in the physical functioning domain (e.g., ability to walk and engage in physical activities) of the CFQ-R at Day 28 (range of scores: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R physical functioning domain score and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Change From Baseline in CFQ-R Physical Functioning Domain Score	-0.69 Units on a scale Standard Error 1.53	1.79 Units on a scale Standard Error 1.57

SECONDARY outcome

Timeframe: Day 0 to Day 42

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

The number of participants requiring additional antipseudomonal antibiotics (oral, intravenous \[IV\], or by inhalation), the time to use of these antibiotics, and the reasons for use was recorded. A binary variable was defined to indicate whether the participants needed any antipseudomonal antibiotics that were non-study drug via the oral, IV, or inhalation route between Day 0 (Baseline Visit) and Day 42 (Visit 5). Fisher's Exact Test was implemented on the intent-to-treat (ITT) and per protocol analysis sets to detect treatment effects on need for additional antipseudomonal antibiotics.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Number of Participants Using Additional (Nonprotocol-specified) Antipseudomonal Antibiotics During Study	21 Participants	19 Participants

SECONDARY outcome

Timeframe: Day 0 to Day 42

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

Hospitalization was defined as any hospital admission lasting for more than 1 calendar day that had been recorded as a serious adverse event (SAE) on the electronic case report form (eCRF). Binary variables were defined to indicate whether participants experienced any hospitalization. Number of hospitalizations was summarized by treatment group.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Number of Participants Hospitalized During Study	3 Study participants	8 Study participants

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 AZLI or placebo). No imputation methods were used for the analysis.

Sputum samples were collected at all study visits for quantitative and qualitative culture for PA. Sputum PA density was quantified by logarithm transformation of the CFU value with base 10. Change from baseline in sputum PA density was calculated as the difference between the log10 CFU values at Day 28 (Visit 4) and the baseline value. Missing data was not imputed. Baseline log10 CFU and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=31 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=37 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 TID using the investigational nebulizer.
Change From Baseline in Log10 Pseudomonas Aeruginosa (PA) Colony Forming Units (CFUs) in Sputum at Day 28	-0.14 Log10 PA CFUs/gram of sputum Standard Error 0.36	-1.35 Log10 PA CFUs/gram of sputum Standard Error 0.36

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 AZLI or placebo). 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 method was used.

Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested by the ANCOVA model using the ITT analysis set. Baseline FEV1 percent predicted and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted	-2.45 Percent change from baseline Standard Error 0.82	0.29 Percent change from baseline Standard Error 0.85

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 AZLI or placebo). No imputation methods were used for the analysis.

Sputum/throat swab samples were collected at all visits for quantitative and qualitative culture of Burkholderia species, Stenotrophomonas maltophilia, Achromobacter xylosidans, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), and Aspergillus species. One CFU on the culture from either a sputum or throat swab sample was considered presence of the particular organism.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Number of Participants Testing Positive for Other Respiratory Pathogens B. cepacia - Day 0	1 Participants	0 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens B. cepacia - Day 28	1 Participants	1 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens S. maltophilia - Day 0	7 Participants	8 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens S. maltophilia - Day 28	9 Participants	8 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens A. xylosoxidans - Day 0	0 Participants	1 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens A. xylosoxidans - Day 28	2 Participants	1 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens MRSA - Day 0	14 Participants	14 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens MRSA - Day 28	13 Participants	13 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens MSSA - Day 0	31 Participants	28 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens MSSA - Day 28	31 Participants	25 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens Aspergillus spp. - Day 0	6 Participants	10 Participants
Number of Participants Testing Positive for Other Respiratory Pathogens Aspergillus spp. - Day 28	6 Participants	11 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 AZLI or placebo).

Aztreonam susceptibility of PA isolates from expectorated sputum samples (collected at all visits) was assessed. The minimum inhibitory concentration (MIC) is the lowest concentration of antimicrobial agent that inhibits visible growth of a microorganism. The MIC50 and MIC90 for PA is the MIC required to inhibit the growth of 50% or 90% of PA isolates, respectively. Given that there might be multiple PA isolates for each participant, the MIC50 and MIC90 for PA was calculated using the MIC values for all PA isolates. The MIC50 and MIC90 were calculated by treatment group.

Outcome measures

Outcome measures
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
The Minimum Concentrations of Aztreonam That Inhibit 50% and 90% of All PA Isolates (MIC50 and MIC90, Respectively) Baseline MIC50	1 µg/mL	1 µg/mL
The Minimum Concentrations of Aztreonam That Inhibit 50% and 90% of All PA Isolates (MIC50 and MIC90, Respectively) Day 28 MIC50	1 µg/mL	4 µg/mL
The Minimum Concentrations of Aztreonam That Inhibit 50% and 90% of All PA Isolates (MIC50 and MIC90, Respectively) Baseline MIC90	16 µg/mL	8 µg/mL
The Minimum Concentrations of Aztreonam That Inhibit 50% and 90% of All PA Isolates (MIC50 and MIC90, Respectively) Day 28 MIC90	16 µg/mL	32 µg/mL

Adverse Events

Placebo Three Times Daily (TID)

Serious events: 3 serious events

Other events: 62 other events

Deaths: 0 deaths

AZLI 75 mg Three Times Daily (TID)

Serious events: 9 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Three Times Daily (TID) n=81 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 TID by inhalation using the investigational nebulizer.	AZLI 75 mg Three Times Daily (TID) n=76 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 TID using the investigational nebulizer.
Gastrointestinal disorders Abdominal pain	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	0.00% 0/76 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Gastrointestinal disorders Abdominal pain upper	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	0.00% 0/76 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Investigations Breath sounds abnormal	0.00% 0/81 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	3.9% 3/76 • Number of events 3 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/81 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/81 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	0.00% 0/76 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Metabolism and nutrition disorders Malnutrition	0.00% 0/81 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Gastrointestinal disorders Melaena	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	0.00% 0/76 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
General disorders Pain	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	0.00% 0/76 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Respiratory, thoracic and mediastinal disorders Pseudomonas bronchitis	0.00% 0/81 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Investigations Pulmonary function test decreased	1.2% 1/81 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
General disorders Pyrexia	2.5% 2/81 • Number of events 2 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
Respiratory, thoracic and mediastinal disorders Sinusitis	0.00% 0/81 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.	1.3% 1/76 • Number of events 1 • Treatment-emergent AEs were collected continuously from the first dose (Day 0) until 14 days after last AZLI/placebo dose (typically Day 42). Participants who discontinued were evaluated for at least 14 days after last dose of study drug. An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by participant at any time during study, whether or not event was considered related to study participation or study procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.

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 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 scholarly 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