Trial Outcomes & Findings for Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis (CF) Patients With Pseudomonas Aeruginosa (PA) (NCT NCT00128492)

Last Updated: 2011-05-19

Results Overview

Participants experiencing at least 1 treatment-emergent AE or at least 1 serious adverse event (SAE) were summarized for the study as a whole. A treatment-emergent AE was any physical or clinical worsening in symptoms or disease experienced by the participant, whether or not the event was considered related to study participation or study procedures. An SAE was any adverse experience that resulted in hospitalization or death. Participants were monitored for AEs and SAEs during all on-treatment and off-treatment intervals throughout the 18-month study period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

274 participants

Primary outcome timeframe

Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Results posted on

2011-05-19

Participant Flow

Open-label, Phase 3 follow-on study for participants from Studies CP-AI-005 (NCT00104520) and CP-AI-007 (NCT00112359). Participants were enrolled at 71 sites in the United States, Canada, Australia, and New Zealand. The date of first enrollment was 17 August 2005, and the date of database lock was 23 January 2009.

Participants enrolled in this study were required to have previously participated in CP-AI-005 or CP-AI-007. Participants from CP-AI-005 received open-label AZLI (75 mg) in the same regimen (twice daily \[BID\] or three times daily \[TID\]) to which they were previously randomized. Participants from CP-AI-007 received open-label AZLI (75 mg) TID.

Participant milestones

Participant milestones
Measure	75 mg AZLI Two Times a Day (BID) Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Overall Study STARTED	85	189
Overall Study COMPLETED	65	130
Overall Study NOT COMPLETED	20	59

Reasons for withdrawal

Reasons for withdrawal
Measure	75 mg AZLI Two Times a Day (BID) Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Overall Study AE unrelated to study	2	9
Overall Study Study drug intolerance (AE)	2	8
Overall Study AE related to study	1	4
Overall Study Death	1	0
Overall Study Lost to Follow-up	1	5
Overall Study Noncompliance	0	5
Overall Study Personal or administrative	10	22
Overall Study Withdrawal by Subject	3	5
Overall Study Pregnancy	0	1

Baseline Characteristics

Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis (CF) Patients With Pseudomonas Aeruginosa (PA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily	Total n=274 Participants Total of all reporting groups
Age, Categorical <=18 years	19 Participants n=5 Participants	36 Participants n=7 Participants	55 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	65 Participants n=5 Participants	151 Participants n=7 Participants	216 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age Continuous	27.3 years STANDARD_DEVIATION 11.4 • n=5 Participants	29.0 years STANDARD_DEVIATION 13.0 • n=7 Participants	28.5 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	89 Participants n=7 Participants	123 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	100 Participants n=7 Participants	151 Participants n=5 Participants
Region of Enrollment United States	85 participants n=5 Participants	157 participants n=7 Participants	242 participants n=5 Participants
Region of Enrollment Canada	0 participants n=5 Participants	8 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Australia	0 participants n=5 Participants	22 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment New Zealand	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA) Aztreonam MIC > 8 µg/mL	30 participants n=5 Participants	72 participants n=7 Participants	102 participants n=5 Participants
Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA) Aztreonam MIC < or = 8 µg/mL	46 participants n=5 Participants	99 participants n=7 Participants	145 participants n=5 Participants
Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA) Unknown	9 participants n=5 Participants	18 participants n=7 Participants	27 participants n=5 Participants
Disease severity as defined by FEV1 percent predicted category FEV1 > 50% predicted	49 Participants n=5 Participants	114 Participants n=7 Participants	163 Participants n=5 Participants
Disease severity as defined by FEV1 percent predicted category FEV1 ≤ 50% predicted	36 Participants n=5 Participants	74 Participants n=7 Participants	110 Participants n=5 Participants
Disease severity as defined by FEV1 percent predicted category Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Body Mass Index (BMI)	21.30 kg/m^2 STANDARD_DEVIATION 3.25 • n=5 Participants	21.44 kg/m^2 STANDARD_DEVIATION 3.96 • n=7 Participants	21.40 kg/m^2 STANDARD_DEVIATION 3.75 • n=5 Participants
Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS)	65.410 Units on a scale STANDARD_DEVIATION 16.896 • n=5 Participants	60.332 Units on a scale STANDARD_DEVIATION 18.497 • n=7 Participants	61.895 Units on a scale STANDARD_DEVIATION 18.141 • n=5 Participants
Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted	56.711 Percent STANDARD_DEVIATION 17.505 • n=5 Participants	55.071 Percent STANDARD_DEVIATION 15.428 • n=7 Participants	55.582 Percent STANDARD_DEVIATION 16.089 • n=5 Participants
Log10 Pseudomonas aeruginosa (PA) Colony-Forming Units (CFUs) in Sputum	5.71 log10 CFUs/g STANDARD_DEVIATION 2.249 • n=5 Participants	6.16 log10 CFUs/g STANDARD_DEVIATION 1.894 • n=7 Participants	6.02 log10 CFUs/g STANDARD_DEVIATION 2.014 • n=5 Participants
Weight	59.52 kg STANDARD_DEVIATION 13.28 • n=5 Participants	59.28 kg STANDARD_DEVIATION 15.81 • n=7 Participants	59.36 kg STANDARD_DEVIATION 15.05 • n=5 Participants

PRIMARY outcome

Timeframe: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Number of Participants Reporting Adverse Events (AEs) Number of Participants Reporting at Least One AE	83 participants	185 participants
Number of Participants Reporting Adverse Events (AEs) Participants Reporting at least One Related AE	30 participants	79 participants
Number of Participants Reporting Adverse Events (AEs) Number of Participants Reporting at Least One SAE	38 participants	100 participants
Number of Participants Reporting Adverse Events (AEs) Participants with Study Drug Withdrawn due to AE	7 participants	38 participants
Number of Participants Reporting Adverse Events (AEs) Number of Participants who Died on Study	1 participants	0 participants

PRIMARY outcome

Timeframe: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Airway reactivity (percent change in FEV1 from pretreatment to 30 minutes after treatment with AZLI) was assessed at all study visits in which a participant received AZLI treatment. A participant was included in this endpoint if they experienced a decline in FEV1 of ≥15% at any visit in which they received AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI Participants with <15% decline	76 Participants	175 Participants
Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI Participants with >=15% decline	9 Participants	14 Participants

PRIMARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

HR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change in Heart Rate (HR) HR, End of Treatment Course 1	1.08 beats/minute Standard Deviation 15.9	-0.07 beats/minute Standard Deviation 12.9
Change in Heart Rate (HR) HR, End of Treatment Course 3	-0.53 beats/minute Standard Deviation 13.7	0.13 beats/minute Standard Deviation 14.5
Change in Heart Rate (HR) HR, End of Treatment Course 9	3.87 beats/minute Standard Deviation 12.9	-0.06 beats/minute Standard Deviation 12.5

PRIMARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

BP was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change in Systolic and Diastolic Blood Pressure (BP) Systolic BP, End of Treatment Course 1	0.75 mm Hg Standard Deviation 11.0	1.19 mm Hg Standard Deviation 11.7
Change in Systolic and Diastolic Blood Pressure (BP) Systolic BP, End of Treatment Course 3	-0.67 mm Hg Standard Deviation 13.1	0.29 mm Hg Standard Deviation 11.9
Change in Systolic and Diastolic Blood Pressure (BP) Systolic BP, End of Treatment Course 9	-1.06 mm Hg Standard Deviation 13.2	-0.33 mm Hg Standard Deviation 11.0
Change in Systolic and Diastolic Blood Pressure (BP) Diastolic BP, End of Treatment Course 1	0.49 mm Hg Standard Deviation 8.4	0.05 mm Hg Standard Deviation 8.2
Change in Systolic and Diastolic Blood Pressure (BP) Diastolic BP, End of Treatment Course 3	-1.64 mm Hg Standard Deviation 8.7	-0.89 mm Hg Standard Deviation 8.3
Change in Systolic and Diastolic Blood Pressure (BP) Diastolic BP, End of Treatment Course 9	-0.40 mm Hg Standard Deviation 9.4	-0.76 mm Hg Standard Deviation 10.0

PRIMARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Temperature was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change in Temperature Temperature (Celsius) End of Treatment Course 1	-0.05 degrees Celsius Standard Deviation 0.4	0.00 degrees Celsius Standard Deviation 0.5
Change in Temperature Temperature (Celsius) End of Treatment Course 3	-0.09 degrees Celsius Standard Deviation 0.4	0.01 degrees Celsius Standard Deviation 0.5
Change in Temperature Temperature (Celsius) End of Treatment Course 9	0.04 degrees Celsius Standard Deviation 0.6	0.05 degrees Celsius Standard Deviation 0.5

PRIMARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

RR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change in Respiratory Rate (RR) RR, End of Treatment Course 1	-0.07 breaths/minute Standard Deviation 2.8	0.17 breaths/minute Standard Deviation 3.9
Change in Respiratory Rate (RR) RR, End of Treatment Course 3	-0.03 breaths/minute Standard Deviation 3.3	0.02 breaths/minute Standard Deviation 3.7
Change in Respiratory Rate (RR) RR, End of Treatment Course 9	0.02 breaths/minute Standard Deviation 3.8	0.33 breaths/minute Standard Deviation 3.3

PRIMARY outcome

Timeframe: Baseline and end of Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI. Results obtained at the end of a 28-day treatment period are presented for selected timepoints.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets WBCs, Baseline	9.28 number of cells x10^3/µL Standard Deviation 3.692	10.11 number of cells x10^3/µL Standard Deviation 3.635
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets WBCs, End of Treatment Course 9	9.47 number of cells x10^3/µL Standard Deviation 3.998	9.53 number of cells x10^3/µL Standard Deviation 3.562
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Basophils, Baseline	0.05 number of cells x10^3/µL Standard Deviation 0.037	0.06 number of cells x10^3/µL Standard Deviation 0.144
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Basophils, End of Treatment Course 9	0.05 number of cells x10^3/µL Standard Deviation 0.034	0.05 number of cells x10^3/µL Standard Deviation 0.033
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Eosinophils, Baseline	0.18 number of cells x10^3/µL Standard Deviation 0.111	0.19 number of cells x10^3/µL Standard Deviation 0.152
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Eosinophils, End of Treatment Course 9	0.21 number of cells x10^3/µL Standard Deviation 0.209	0.17 number of cells x10^3/µL Standard Deviation 0.144
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Lymphocytes, Baseline	2.00 number of cells x10^3/µL Standard Deviation 0.623	2.17 number of cells x10^3/µL Standard Deviation 0.732
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Lymphocytes, End of Treatment Course 9	1.99 number of cells x10^3/µL Standard Deviation 0.801	2.13 number of cells x10^3/µL Standard Deviation 0.719
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Monocytes, Baseline	0.47 number of cells x10^3/µL Standard Deviation 0.190	0.54 number of cells x10^3/µL Standard Deviation 0.241
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Monocytes, End of Treatment Course 9	0.50 number of cells x10^3/µL Standard Deviation 0.157	0.52 number of cells x10^3/µL Standard Deviation 0.210
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Neutrophils, Baseline	6.54 number of cells x10^3/µL Standard Deviation 3.295	7.09 number of cells x10^3/µL Standard Deviation 3.227
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Neutrophils, End of Treatment Course 9	6.68 number of cells x10^3/µL Standard Deviation 3.481	6.63 number of cells x10^3/µL Standard Deviation 3.345
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Platelets, Baseline	293.11 number of cells x10^3/µL Standard Deviation 85.681	340.19 number of cells x10^3/µL Standard Deviation 106.749
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets Platelets, End of Treatment Course 9	290.43 number of cells x10^3/µL Standard Deviation 106.903	311.39 number of cells x10^3/µL Standard Deviation 98.370

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Basophils, Baseline	0.59 percent of differential Standard Deviation 0.379	0.61 percent of differential Standard Deviation 0.390
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Basophils, End of Treatment Course 9	0.59 percent of differential Standard Deviation 0.393	0.62 percent of differential Standard Deviation 0.340
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Eosinophils, Baseline	2.05 percent of differential Standard Deviation 1.194	1.95 percent of differential Standard Deviation 1.453
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Eosinophils, End of Treatment Course 9	2.20 percent of differential Standard Deviation 1.694	1.88 percent of differential Standard Deviation 1.625
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Lymphocytes, Baseline	23.40 percent of differential Standard Deviation 8.278	22.74 percent of differential Standard Deviation 8.265
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Lymphocytes, End of Treatment Course 9	22.30 percent of differential Standard Deviation 7.462	24.17 percent of differential Standard Deviation 8.441
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Monocytes, Baseline	5.32 percent of differential Standard Deviation 1.919	5.26 percent of differential Standard Deviation 1.752
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Monocytes, End of Treatment Course 9	5.64 percent of differential Standard Deviation 1.660	5.77 percent of differential Standard Deviation 1.977
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Neutrophils, Baseline	68.39 percent of differential Standard Deviation 9.331	69.26 percent of differential Standard Deviation 9.261
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Neutrophils, End of Treatment Course 9	69.02 percent of differential Standard Deviation 8.551	67.46 percent of differential Standard Deviation 9.808

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Number of Red Blood Cells (RBC) RBCs, Baseline	5.15 number x10^6/µL Standard Deviation 0.442	4.94 number x10^6/µL Standard Deviation 0.499
Serum Hematology - Number of Red Blood Cells (RBC) RBCs, End of treatment 9	4.93 number x10^6/µL Standard Deviation 0.376	4.77 number x10^6/µL Standard Deviation 0.492

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Hematocrit Hematocrit, Baseline	43.43 percent Standard Deviation 4.037	42.45 percent Standard Deviation 4.142
Serum Hematology - Hematocrit Hematocrit, End of treatment course 9	42.00 percent Standard Deviation 3.317	41.63 percent Standard Deviation 4.056

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Hemoglobin Hemoglobin, Baseline	14.06 g/dL Standard Deviation 1.406	13.70 g/dL Standard Deviation 1.448
Serum Hematology - Hemoglobin Hemoglobin, End of treatment course 9	13.89 g/dL Standard Deviation 1.195	13.71 g/dL Standard Deviation 1.475

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Mean Corpuscular Volume (MCV) MCV, Baseline	84.33 fL Standard Deviation 4.880	86.08 fL Standard Deviation 5.560
Serum Hematology - Mean Corpuscular Volume (MCV) MCV, End of treatment course 9	85.38 fL Standard Deviation 5.232	87.72 fL Standard Deviation 5.450

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Mean Corpuscular Hemoglobin (MCH) MCH, Baseline	27.43 pg Standard Deviation 1.824	27.84 pg Standard Deviation 2.090
Serum Hematology - Mean Corpuscular Hemoglobin (MCH) MCH, End of treatment course 9	28.35 pg Standard Deviation 2.282	28.89 pg Standard Deviation 2.050

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) MCHC, Baseline	32.41 g/dL Standard Deviation 1.032	32.34 g/dL Standard Deviation 1.228
Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) MCHC, End of treatment course 9	33.13 g/dL Standard Deviation 1.272	32.99 g/dL Standard Deviation 1.288

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) ALT, Baseline	31.21 U/L Standard Deviation 22.343	26.65 U/L Standard Deviation 18.982
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) ALT, End of Treatment Course 9	30.78 U/L Standard Deviation 24.045	27.81 U/L Standard Deviation 21.794
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) AST, Baseline	27.83 U/L Standard Deviation 14.856	25.77 U/L Standard Deviation 15.556
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) AST, End of Treatment Course 9	26.84 U/L Standard Deviation 14.588	26.22 U/L Standard Deviation 15.240
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) GGT, Baseline	35.49 U/L Standard Deviation 48.215	29.64 U/L Standard Deviation 41.862
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) GGT, End of Treatment Course 9	40.83 U/L Standard Deviation 57.471	32.39 U/L Standard Deviation 39.662

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Calcium (EDTA), Baseline	9.67 mg/dL Standard Deviation 0.406	9.56 mg/dL Standard Deviation 0.416
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Calcium (EDTA), End of Treatment Course 9	9.43 mg/dL Standard Deviation 0.385	9.47 mg/dL Standard Deviation 0.427
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Creatinine, Baseline	0.80 mg/dL Standard Deviation 0.202	0.81 mg/dL Standard Deviation 0.317
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Creatinine, End of Treatment Course 9	0.80 mg/dL Standard Deviation 0.207	0.82 mg/dL Standard Deviation 0.295
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Direct bilirubin, Baseline	0.14 mg/dL Standard Deviation 0.076	0.13 mg/dL Standard Deviation 0.064
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Direct bilirubin, End of Treatment Course 9	0.16 mg/dL Standard Deviation 0.081	0.14 mg/dL Standard Deviation 0.072
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Total bilirubin, Baseline	0.42 mg/dL Standard Deviation 0.237	0.43 mg/dL Standard Deviation 0.298
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Total bilirubin, End of Treatment Course 9	0.51 mg/dL Standard Deviation 0.294	0.49 mg/dL Standard Deviation 0.377
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Serum glucose, Baseline	115.46 mg/dL Standard Deviation 55.211	111.53 mg/dL Standard Deviation 49.485
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen Serum glucose, End of Treatment Course 9	121.11 mg/dL Standard Deviation 57.47	116.40 mg/dL Standard Deviation 65.046
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen BUN, Baseline	14.65 mg/dL Standard Deviation 4.258	14.32 mg/dL Standard Deviation 5.698
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen BUN, End of Treatment Course 9	13.83 mg/dL Standard Deviation 4.764	14.49 mg/dL Standard Deviation 4.805

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium Serum chloride, Baseline	102.17 mEq/L Standard Deviation 2.904	102.22 mEq/L Standard Deviation 2.943
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium Serum chloride, End of Treatment Course 9	101.81 mEq/L Standard Deviation 2.610	102.16 mEq/L Standard Deviation 2.977
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium Serum potassium, Baseline	4.20 mEq/L Standard Deviation 0.354	4.29 mEq/L Standard Deviation 0.370
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium Serum potassium, End of Treatment Course 9	4.19 mEq/L Standard Deviation 0.388	4.25 mEq/L Standard Deviation 0.372
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium Serum sodium, Baseline	139.18 mEq/L Standard Deviation 2.984	139.23 mEq/L Standard Deviation 2.618
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium Serum sodium, End of Treatment Course 9	138.64 mEq/L Standard Deviation 2.608	138.88 mEq/L Standard Deviation 2.694

PRIMARY outcome

Timeframe: Baseline and end of treatment Course 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Serum Chemistry - Concentration of Total Protein Total protein, Baseline	7.63 g/dL Standard Deviation 0.588	7.58 g/dL Standard Deviation 0.536
Serum Chemistry - Concentration of Total Protein Total protein, End of Treatment Course 9	7.47 g/dL Standard Deviation 0.425	7.53 g/dL Standard Deviation 0.560

SECONDARY outcome

Timeframe: Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

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

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum End of Treatment Course 1	-0.20 Log10 PA CFUs/g Standard Deviation 1.5	-0.81 Log10 PA CFUs/g Standard Deviation 1.8
Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum End of Treatment Course 3	-0.43 Log10 PA CFUs/g Standard Deviation 1.4	-0.53 Log10 PA CFUs/g Standard Deviation 2.1
Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum End of Treatment Course 9	-0.47 Log10 PA CFUs/g Standard Deviation 1.9	-0.60 Log10 PA CFUs/g Standard Deviation 2.1

SECONDARY outcome

Timeframe: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Sputum samples were collected at all study visits for qualitative and quantitative culture for Burkholderia cepacia complex (BCC), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Staphylococcus aureus (including methicillin-sensitive \[MSSA\] and methicillin-resistant \[MRSA\] S.aureus), and fungal organisms. Number of participants with other pathogens at baseline and end of AZLI treatment Courses 1, 3, and 9 are reported.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Number of Participants With Other Pathogens BCC, Follow-up	0 Participants	1 Participants
Number of Participants With Other Pathogens A. xylosoxidans, Baseline	8 Participants	13 Participants
Number of Participants With Other Pathogens Aspergillus Species, End of Treatment Course 1	18 Participants	35 Participants
Number of Participants With Other Pathogens Aspergillus Species, End of Treatment Course 3	21 Participants	33 Participants
Number of Participants With Other Pathogens Aspergillus Species, End of Treatment Course 9	9 Participants	27 Participants
Number of Participants With Other Pathogens Aspergillus Species, Follow-up	10 Participants	38 Participants
Number of Participants With Other Pathogens Candida Species, End of Treatment Course 3	55 Participants	125 Participants
Number of Participants With Other Pathogens Candida Species, End of Treatment Course 9	38 Participants	101 Participants
Number of Participants With Other Pathogens S. aureus, Baseline	33 Participants	65 Participants
Number of Participants With Other Pathogens S. aureus, End of Treatment Course 1	34 Participants	66 Participants
Number of Participants With Other Pathogens S. aureus, End of Treatment Course 3	41 Participants	68 Participants
Number of Participants With Other Pathogens S. aureus, End of Treatment Course 9	15 Participants	51 Participants
Number of Participants With Other Pathogens S. aureus, Follow-up	16 Participants	49 Participants
Number of Participants With Other Pathogens MSSA, Baseline	26 Participants	32 Participants
Number of Participants With Other Pathogens MSSA, End of Treatment Course 1	27 Participants	32 Participants
Number of Participants With Other Pathogens MSSA, End of Treatment Course 3	31 Participants	35 Participants
Number of Participants With Other Pathogens MSSA, End of Treatment Course 9	10 Participants	31 Participants
Number of Participants With Other Pathogens MSSA, Follow-up	11 Participants	32 Participants
Number of Participants With Other Pathogens MRSA, Baseline	7 Participants	25 Participants
Number of Participants With Other Pathogens MRSA, End of Treatment Course 1	7 Participants	25 Participants
Number of Participants With Other Pathogens MRSA, End of Treatment Course 3	9 Participants	26 Participants
Number of Participants With Other Pathogens MRSA, End of Treatment Course 9	5 Participants	19 Participants
Number of Participants With Other Pathogens MRSA, Follow-up	5 Participants	17 Participants
Number of Participants With Other Pathogens BCC, Baseline	0 Participants	1 Participants
Number of Participants With Other Pathogens BCC, End of Treatment Course 1	0 Participants	0 Participants
Number of Participants With Other Pathogens BCC, End of Treatment Course 3	0 Participants	1 Participants
Number of Participants With Other Pathogens Candida Species, Baseline	51 Participants	135 Participants
Number of Participants With Other Pathogens Candida Species, End of Treatment Course 1	48 Participants	139 Participants
Number of Participants With Other Pathogens Candida Species, Follow-up	36 Participants	95 Participants
Number of Participants With Other Pathogens BCC, End of Treatment Course 9	0 Participants	0 Participants
Number of Participants With Other Pathogens S. maltophilia, Baseline	13 Participants	14 Participants
Number of Participants With Other Pathogens S. maltophilia, End of Treatment Course 1	12 Participants	17 Participants
Number of Participants With Other Pathogens S. maltophilia, End of Treatment Course 3	11 Participants	15 Participants
Number of Participants With Other Pathogens S. maltophilia, End of Treatment Course 9	5 Participants	14 Participants
Number of Participants With Other Pathogens S. maltophilia, Follow-up	6 Participants	12 Participants
Number of Participants With Other Pathogens A. xylosoxidans, End of Treatment Course 1	8 Participants	11 Participants
Number of Participants With Other Pathogens A. xylosoxidans, End of Treatment Course 3	7 Participants	12 Participants
Number of Participants With Other Pathogens A. xylosoxidans, End of Treatment Course 9	4 Participants	9 Participants
Number of Participants With Other Pathogens A. xylosoxidans, Follow-up	4 Participants	7 Participants
Number of Participants With Other Pathogens Aspergillus Species, Baseline	15 Participants	41 Participants

SECONDARY outcome

Timeframe: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

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

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC50, End of Treatment Course 9	16 µg/mL	8 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC50, Baseline	4 µg/mL	4 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC50, End of Treatment Course 1	4 µg/mL	8 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC50, End of Treatment Course 3	8 µg/mL	8 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC50, Follow-up	4 µg/mL	8 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC90, Baseline	128 µg/mL	128 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC90, End of Treatment Course 1	256 µg/mL	256 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC90, End of Treatment Course 3	256 µg/mL	256 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC90, End of Treatment Course 9	512 µg/mL	512 µg/mL
Minimum Inhibitory Concentration (MIC) of Aztreonam MIC90, Follow-up	128 µg/mL	256 µg/mL

SECONDARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air exhaled in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudson equation, based upon participant age, gender, and height. FVC = (forced vital capacity) the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. The percent change from baseline is presented for each endpoint.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEV1 (L), End of Treatment Course 1	4.87 Percent change from baseline Standard Deviation 11.428	7.98 Percent change from baseline Standard Deviation 16.512
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEV1 (L), End of Treatment Course 3	3.55 Percent change from baseline Standard Deviation 12.491	6.04 Percent change from baseline Standard Deviation 16.489
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FVC (L), End of Treatment Course 1	3.13 Percent change from baseline Standard Deviation 11.946	5.59 Percent change from baseline Standard Deviation 16.533
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEV1 (L), End of Treatment Course 9	1.31 Percent change from baseline Standard Deviation 15.924	3.98 Percent change from baseline Standard Deviation 17.899
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEV1 Percent Predicted, End of Treatment Course 1	4.91 Percent change from baseline Standard Deviation 11.599	7.97 Percent change from baseline Standard Deviation 16.511
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEV1 Percent Predicted, End of Treatment Course 3	3.46 Percent change from baseline Standard Deviation 12.504	6.15 Percent change from baseline Standard Deviation 16.592
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEV1 Percent Predicted, End of Treatment Course 9	1.23 Percent change from baseline Standard Deviation 15.673	4.24 Percent change from baseline Standard Deviation 17.992
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FVC (L), End of Treatment Course 3	1.77 Percent change from baseline Standard Deviation 10.948	5.95 Percent change from baseline Standard Deviation 13.178
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FVC (L), End of Treatment Course 9	1.51 Percent change from baseline Standard Deviation 14.150	5.29 Percent change from baseline Standard Deviation 14.075
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEF25-75 (L/sec), End of Treatment Course 1	12.81 Percent change from baseline Standard Deviation 36.149	14.14 Percent change from baseline Standard Deviation 36.089
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEF25-75 (L/sec), End of Treatment Course 3	16.05 Percent change from baseline Standard Deviation 55.447	4.81 Percent change from baseline Standard Deviation 32.579
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) FEF25-75 (L/sec), End of Treatment Course 9	3.24 Percent change from baseline Standard Deviation 28.506	3.29 Percent change from baseline Standard Deviation 36.329

SECONDARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms). The minimal clinically important difference (MCID) corresponds to the smallest change in symptoms that a patient can detect and is a change in score of 4 points.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) End of Treatment Course 3	0.37 Units on a scale Standard Deviation 19.296	7.34 Units on a scale Standard Deviation 18.518
Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) End of Treatment Course 1	3.53 Units on a scale Standard Deviation 12.243	6.83 Units on a scale Standard Deviation 17.379
Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) End of Treatment Course 9	0.30 Units on a scale Standard Deviation 15.217	6.01 Units on a scale Standard Deviation 17.943

SECONDARY outcome

Timeframe: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Details of all hospitalizations, including the dates of admission and discharge, were recorded on the serious adverse event (SAE) electronic case report form (eCRF). Time to first hospitalization was the number of days from baseline (Visit 1) to the date of first hospitalization or the date of study completion (last visit) /or early withdrawal if censored.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Time to First Hospitalization Due to a Respiratory Event	359 Days Full Range 27.60 • Interval 4.0 to 431.0	417 Days Full Range 21.32 • Interval 1.0 to 609.0

SECONDARY outcome

Timeframe: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Weight was measured at all visits and was reported to the nearest 0.1 kg/lb. Percent change in weight from baseline was calculated.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Change in Body Weight End of Treatment Course 1	0.58 Percent change from baseline Standard Error 2.449	0.85 Percent change from baseline Standard Error 2.338
Change in Body Weight End of Treatment Course 3	1.31 Percent change from baseline Standard Error 3.769	1.38 Percent change from baseline Standard Error 3.991
Change in Body Weight End of Treatment Course 9	3.24 Percent change from baseline Standard Error 6.542	3.55 Percent change from baseline Standard Error 7.431

SECONDARY outcome

Timeframe: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Participants were provided with a diary card at each visit to record days of work and/or school missed due to their CF symptoms. The percentage of school/work days missed was calculated as the total number of school/work days missed divided by the total number of on-study days multiplied by 100 across all participants in a treatment group.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Missed School/Work Days Due to CF Symptoms	2.00 Percentage of days missed Standard Deviation 4.04	3.19 Percentage of days missed Standard Deviation 6.86

SECONDARY outcome

Timeframe: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.

Use of IV antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF. The time to first IV antipseudomonal antibiotic use was the number of days from baseline (Visit 1) to the date of first IV antipseudomonal antibiotic use or the date of study completion (last visit) /or early withdrawal if censored.

Outcome measures

Outcome measures
Measure	75 mg AZLI Two Times a Day (BID) n=85 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. BID = twice daily	75 mg AZLI Three Times a Day (TID) n=189 Participants Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy. TID = three times daily
Time to Intravenous (IV) Antipseudomonal Antibiotics	276 Days Interval 217.0 to 316.0	232 Days Interval 179.0 to 288.0

Adverse Events

75 mg AZLI Two Times a Day (BID)

Serious events: 38 serious events

Other events: 83 other events

Deaths: 0 deaths

75 mg AZLI Three Times a Day (TID)

Serious events: 100 serious events

Other events: 185 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mark Bresnik, Director of Clinical Research

Gilead Sciences, Inc.

Phone: 650-522-5934

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER