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Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis (CF) Patients With Pseudomonas Aeruginosa (PA) (AIR-CF3)

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ClinicalTrials.gov Identifier: NCT00128492
Recruitment Status : Completed
First Posted : August 10, 2005
Results First Posted : March 11, 2011
Last Update Posted : May 19, 2011
Sponsor:
Information provided by:
Gilead Sciences

Study Type Interventional
Study Design Allocation: Non-Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Intervention Drug: AZLI 75 mg two times a day (BID)/ three times a day (TID)
Enrollment 274
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description

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

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

Period Title: Overall Study
Started 85 189
Completed 65 130
Not Completed 20 59
Reason Not Completed
AE unrelated to study             2             9
Study drug intolerance (AE)             2             8
AE related to study             1             4
Death             1             0
Lost to Follow-up             1             5
Noncompliance             0             5
Personal or administrative             10             22
Withdrawal by Subject             3             5
Pregnancy             0             1
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID) Total
Hide Arm/Group Description

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

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 of all reporting groups
Overall Number of Baseline Participants 85 189 274
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 189 participants 274 participants
<=18 years
19
  22.4%
36
  19.0%
55
  20.1%
Between 18 and 65 years
65
  76.5%
151
  79.9%
216
  78.8%
>=65 years
1
   1.2%
2
   1.1%
3
   1.1%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants 189 participants 274 participants
27.3  (11.4) 29.0  (13.0) 28.5  (12.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 189 participants 274 participants
Female
34
  40.0%
89
  47.1%
123
  44.9%
Male
51
  60.0%
100
  52.9%
151
  55.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 189 participants 274 participants
United States 85 157 242
Canada 0 8 8
Australia 0 22 22
New Zealand 0 2 2
Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 189 participants 274 participants
Aztreonam MIC > 8 µg/mL 30 72 102
Aztreonam MIC < or = 8 µg/mL 46 99 145
Unknown 9 18 27
[1]
Measure Description: Number of partipipants with an MIC of aztreonam ≤ 8 µg/mL or >8 µg/mL for PA are summarized.
Disease severity as defined by FEV1 percent predicted category   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 189 participants 274 participants
FEV1 > 50% predicted 49 114 163
FEV1 ≤ 50% predicted 36 74 110
Unknown 0 1 1
[1]
Measure Description: FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. This baseline measure indicates the number of subjects with FEV1 greater than 50% and less than or equal to 50% of the predicted value based on age, gender, and height at screening.
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 85 participants 189 participants 274 participants
21.30  (3.25) 21.44  (3.96) 21.40  (3.75)
Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 85 participants 189 participants 274 participants
65.410  (16.896) 60.332  (18.497) 61.895  (18.141)
[1]
Measure Description: CFQ-R RSS scale range 0-100, with higher scores indicating fewer CF symptoms.
Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 85 participants 189 participants 274 participants
56.711  (17.505) 55.071  (15.428) 55.582  (16.089)
[1]
Measure Description: FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height.
Log10 Pseudomonas aeruginosa (PA) Colony-Forming Units (CFUs) in Sputum  
Mean (Standard Deviation)
Unit of measure:  Log10 CFUs/g
Number Analyzed 85 participants 189 participants 274 participants
5.71  (2.249) 6.16  (1.894) 6.02  (2.014)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 85 participants 189 participants 274 participants
59.52  (13.28) 59.28  (15.81) 59.36  (15.05)
1.Primary Outcome
Title Number of Participants Reporting Adverse Events (AEs)
Hide Description

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.

Time Frame Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Measure Type: Number
Unit of Measure: participants
Number of Participants Reporting at Least One AE 83 185
Participants Reporting at least One Related AE 30 79
Number of Participants Reporting at Least One SAE 38 100
Participants with Study Drug Withdrawn due to AE 7 38
Number of Participants who Died on Study 1 0
2.Primary Outcome
Title 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
Hide Description 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.
Time Frame Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Measure Type: Number
Unit of Measure: Participants
Participants with <15% decline 76 175
Participants with >=15% decline 9 14
3.Primary Outcome
Title Change in Heart Rate (HR)
Hide Description

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.

Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: beats/minute
HR, End of Treatment Course 1 1.08  (15.9) -0.07  (12.9)
HR, End of Treatment Course 3 -0.53  (13.7) 0.13  (14.5)
HR, End of Treatment Course 9 3.87  (12.9) -0.06  (12.5)
4.Primary Outcome
Title Change in Systolic and Diastolic Blood Pressure (BP)
Hide Description

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.

Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: mm Hg
Systolic BP, End of Treatment Course 1 0.75  (11.0) 1.19  (11.7)
Systolic BP, End of Treatment Course 3 -0.67  (13.1) 0.29  (11.9)
Systolic BP, End of Treatment Course 9 -1.06  (13.2) -0.33  (11.0)
Diastolic BP, End of Treatment Course 1 0.49  (8.4) 0.05  (8.2)
Diastolic BP, End of Treatment Course 3 -1.64  (8.7) -0.89  (8.3)
Diastolic BP, End of Treatment Course 9 -0.40  (9.4) -0.76  (10.0)
5.Primary Outcome
Title Change in Temperature
Hide Description

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.

Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: degrees Celsius
Temperature (Celsius) End of Treatment Course 1 -0.05  (0.4) 0.00  (0.5)
Temperature (Celsius) End of Treatment Course 3 -0.09  (0.4) 0.01  (0.5)
Temperature (Celsius) End of Treatment Course 9 0.04  (0.6) 0.05  (0.5)
6.Primary Outcome
Title Change in Respiratory Rate (RR)
Hide Description

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.

Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: breaths/minute
RR, End of Treatment Course 1 -0.07  (2.8) 0.17  (3.9)
RR, End of Treatment Course 3 -0.03  (3.3) 0.02  (3.7)
RR, End of Treatment Course 9 0.02  (3.8) 0.33  (3.3)
7.Primary Outcome
Title Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets
Hide Description [Not Specified]
Time Frame Baseline and end of Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: number of cells x10^3/µL
WBCs, Baseline 9.28  (3.692) 10.11  (3.635)
WBCs, End of Treatment Course 9 9.47  (3.998) 9.53  (3.562)
Basophils, Baseline 0.05  (0.037) 0.06  (0.144)
Basophils, End of Treatment Course 9 0.05  (0.034) 0.05  (0.033)
Eosinophils, Baseline 0.18  (0.111) 0.19  (0.152)
Eosinophils, End of Treatment Course 9 0.21  (0.209) 0.17  (0.144)
Lymphocytes, Baseline 2.00  (0.623) 2.17  (0.732)
Lymphocytes, End of Treatment Course 9 1.99  (0.801) 2.13  (0.719)
Monocytes, Baseline 0.47  (0.190) 0.54  (0.241)
Monocytes, End of Treatment Course 9 0.50  (0.157) 0.52  (0.210)
Neutrophils, Baseline 6.54  (3.295) 7.09  (3.227)
Neutrophils, End of Treatment Course 9 6.68  (3.481) 6.63  (3.345)
Platelets, Baseline 293.11  (85.681) 340.19  (106.749)
Platelets, End of Treatment Course 9 290.43  (106.903) 311.39  (98.370)
8.Primary Outcome
Title Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: percent of differential
Basophils, Baseline 0.59  (0.379) 0.61  (0.390)
Basophils, End of Treatment Course 9 0.59  (0.393) 0.62  (0.340)
Eosinophils, Baseline 2.05  (1.194) 1.95  (1.453)
Eosinophils, End of Treatment Course 9 2.20  (1.694) 1.88  (1.625)
Lymphocytes, Baseline 23.40  (8.278) 22.74  (8.265)
Lymphocytes, End of Treatment Course 9 22.30  (7.462) 24.17  (8.441)
Monocytes, Baseline 5.32  (1.919) 5.26  (1.752)
Monocytes, End of Treatment Course 9 5.64  (1.660) 5.77  (1.977)
Neutrophils, Baseline 68.39  (9.331) 69.26  (9.261)
Neutrophils, End of Treatment Course 9 69.02  (8.551) 67.46  (9.808)
9.Primary Outcome
Title Serum Hematology - Number of Red Blood Cells (RBC)
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: number x10^6/µL
RBCs, Baseline 5.15  (0.442) 4.94  (0.499)
RBCs, End of treatment 9 4.93  (0.376) 4.77  (0.492)
10.Primary Outcome
Title Serum Hematology - Hematocrit
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: percent
Hematocrit, Baseline 43.43  (4.037) 42.45  (4.142)
Hematocrit, End of treatment course 9 42.00  (3.317) 41.63  (4.056)
11.Primary Outcome
Title Serum Hematology - Hemoglobin
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: g/dL
Hemoglobin, Baseline 14.06  (1.406) 13.70  (1.448)
Hemoglobin, End of treatment course 9 13.89  (1.195) 13.71  (1.475)
12.Primary Outcome
Title Serum Hematology - Mean Corpuscular Volume (MCV)
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: fL
MCV, Baseline 84.33  (4.880) 86.08  (5.560)
MCV, End of treatment course 9 85.38  (5.232) 87.72  (5.450)
13.Primary Outcome
Title Serum Hematology - Mean Corpuscular Hemoglobin (MCH)
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: pg
MCH, Baseline 27.43  (1.824) 27.84  (2.090)
MCH, End of treatment course 9 28.35  (2.282) 28.89  (2.050)
14.Primary Outcome
Title Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: g/dL
MCHC, Baseline 32.41  (1.032) 32.34  (1.228)
MCHC, End of treatment course 9 33.13  (1.272) 32.99  (1.288)
15.Primary Outcome
Title Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: U/L
ALT, Baseline 31.21  (22.343) 26.65  (18.982)
ALT, End of Treatment Course 9 30.78  (24.045) 27.81  (21.794)
AST, Baseline 27.83  (14.856) 25.77  (15.556)
AST, End of Treatment Course 9 26.84  (14.588) 26.22  (15.240)
GGT, Baseline 35.49  (48.215) 29.64  (41.862)
GGT, End of Treatment Course 9 40.83  (57.471) 32.39  (39.662)
16.Primary Outcome
Title Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: mg/dL
Calcium (EDTA), Baseline 9.67  (0.406) 9.56  (0.416)
Calcium (EDTA), End of Treatment Course 9 9.43  (0.385) 9.47  (0.427)
Creatinine, Baseline 0.80  (0.202) 0.81  (0.317)
Creatinine, End of Treatment Course 9 0.80  (0.207) 0.82  (0.295)
Direct bilirubin, Baseline 0.14  (0.076) 0.13  (0.064)
Direct bilirubin, End of Treatment Course 9 0.16  (0.081) 0.14  (0.072)
Total bilirubin, Baseline 0.42  (0.237) 0.43  (0.298)
Total bilirubin, End of Treatment Course 9 0.51  (0.294) 0.49  (0.377)
Serum glucose, Baseline 115.46  (55.211) 111.53  (49.485)
Serum glucose, End of Treatment Course 9 121.11  (57.47) 116.40  (65.046)
BUN, Baseline 14.65  (4.258) 14.32  (5.698)
BUN, End of Treatment Course 9 13.83  (4.764) 14.49  (4.805)
17.Primary Outcome
Title Serum Chemistry - Concentration of Chloride, Potassium, and Sodium
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: mEq/L
Serum chloride, Baseline 102.17  (2.904) 102.22  (2.943)
Serum chloride, End of Treatment Course 9 101.81  (2.610) 102.16  (2.977)
Serum potassium, Baseline 4.20  (0.354) 4.29  (0.370)
Serum potassium, End of Treatment Course 9 4.19  (0.388) 4.25  (0.372)
Serum sodium, Baseline 139.18  (2.984) 139.23  (2.618)
Serum sodium, End of Treatment Course 9 138.64  (2.608) 138.88  (2.694)
18.Primary Outcome
Title Serum Chemistry - Concentration of Total Protein
Hide Description [Not Specified]
Time Frame Baseline and end of treatment Course 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: g/dL
Total protein, Baseline 7.63  (0.588) 7.58  (0.536)
Total protein, End of Treatment Course 9 7.47  (0.425) 7.53  (0.560)
19.Secondary Outcome
Title Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum
Hide Description

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.

Time Frame Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: Log10 PA CFUs/g
End of Treatment Course 1 -0.20  (1.5) -0.81  (1.8)
End of Treatment Course 3 -0.43  (1.4) -0.53  (2.1)
End of Treatment Course 9 -0.47  (1.9) -0.60  (2.1)
20.Secondary Outcome
Title Number of Participants With Other Pathogens
Hide Description

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.

Time Frame Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Measure Type: Number
Unit of Measure: Participants
S. aureus, Baseline 33 65
S. aureus, End of Treatment Course 1 34 66
S. aureus, End of Treatment Course 3 41 68
S. aureus, End of Treatment Course 9 15 51
S. aureus, Follow-up 16 49
MSSA, Baseline 26 32
MSSA, End of Treatment Course 1 27 32
MSSA, End of Treatment Course 3 31 35
MSSA, End of Treatment Course 9 10 31
MSSA, Follow-up 11 32
MRSA, Baseline 7 25
MRSA, End of Treatment Course 1 7 25
MRSA, End of Treatment Course 3 9 26
MRSA, End of Treatment Course 9 5 19
MRSA, Follow-up 5 17
BCC, Baseline 0 1
BCC, End of Treatment Course 1 0 0
BCC, End of Treatment Course 3 0 1
BCC, End of Treatment Course 9 0 0
BCC, Follow-up 0 1
S. maltophilia, Baseline 13 14
S. maltophilia, End of Treatment Course 1 12 17
S. maltophilia, End of Treatment Course 3 11 15
S. maltophilia, End of Treatment Course 9 5 14
S. maltophilia, Follow-up 6 12
A. xylosoxidans, Baseline 8 13
A. xylosoxidans, End of Treatment Course 1 8 11
A. xylosoxidans, End of Treatment Course 3 7 12
A. xylosoxidans, End of Treatment Course 9 4 9
A. xylosoxidans, Follow-up 4 7
Aspergillus Species, Baseline 15 41
Aspergillus Species, End of Treatment Course 1 18 35
Aspergillus Species, End of Treatment Course 3 21 33
Aspergillus Species, End of Treatment Course 9 9 27
Aspergillus Species, Follow-up 10 38
Candida Species, Baseline 51 135
Candida Species, End of Treatment Course 1 48 139
Candida Species, End of Treatment Course 3 55 125
Candida Species, End of Treatment Course 9 38 101
Candida Species, Follow-up 36 95
21.Secondary Outcome
Title Minimum Inhibitory Concentration (MIC) of Aztreonam
Hide Description

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.

Time Frame Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Measure Type: Number
Unit of Measure: µg/mL
MIC50, Baseline 4 4
MIC50, End of Treatment Course 1 4 8
MIC50, End of Treatment Course 3 8 8
MIC50, End of Treatment Course 9 16 8
MIC50, Follow-up 4 8
MIC90, Baseline 128 128
MIC90, End of Treatment Course 1 256 256
MIC90, End of Treatment Course 3 256 256
MIC90, End of Treatment Course 9 512 512
MIC90, Follow-up 128 256
22.Secondary Outcome
Title Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75)
Hide Description

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.

Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: Percent change from baseline
FEV1 (L), End of Treatment Course 1 4.87  (11.428) 7.98  (16.512)
FEV1 (L), End of Treatment Course 3 3.55  (12.491) 6.04  (16.489)
FEV1 (L), End of Treatment Course 9 1.31  (15.924) 3.98  (17.899)
FEV1 Percent Predicted, End of Treatment Course 1 4.91  (11.599) 7.97  (16.511)
FEV1 Percent Predicted, End of Treatment Course 3 3.46  (12.504) 6.15  (16.592)
FEV1 Percent Predicted, End of Treatment Course 9 1.23  (15.673) 4.24  (17.992)
FVC (L), End of Treatment Course 1 3.13  (11.946) 5.59  (16.533)
FVC (L), End of Treatment Course 3 1.77  (10.948) 5.95  (13.178)
FVC (L), End of Treatment Course 9 1.51  (14.150) 5.29  (14.075)
FEF25-75 (L/sec), End of Treatment Course 1 12.81  (36.149) 14.14  (36.089)
FEF25-75 (L/sec), End of Treatment Course 3 16.05  (55.447) 4.81  (32.579)
FEF25-75 (L/sec), End of Treatment Course 9 3.24  (28.506) 3.29  (36.329)
23.Secondary Outcome
Title Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS)
Hide Description 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.
Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: Units on a scale
End of Treatment Course 1 3.53  (12.243) 6.83  (17.379)
End of Treatment Course 3 0.37  (19.296) 7.34  (18.518)
End of Treatment Course 9 0.30  (15.217) 6.01  (17.943)
24.Secondary Outcome
Title Time to First Hospitalization Due to a Respiratory Event
Hide Description

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.

Time Frame Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Median (Full Range)
Unit of Measure: Days
359
(4 to 431)
417
(1 to 609)
25.Secondary Outcome
Title Change in Body Weight
Hide Description Weight was measured at all visits and was reported to the nearest 0.1 kg/lb. Percent change in weight from baseline was calculated.
Time Frame Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Error)
Unit of Measure: Percent change from baseline
End of Treatment Course 1 0.58  (2.449) 0.85  (2.338)
End of Treatment Course 3 1.31  (3.769) 1.38  (3.991)
End of Treatment Course 9 3.24  (6.542) 3.55  (7.431)
26.Secondary Outcome
Title Missed School/Work Days Due to CF Symptoms
Hide Description

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.

Time Frame Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Mean (Standard Deviation)
Unit of Measure: Percentage of days missed
2.00  (4.04) 3.19  (6.86)
27.Secondary Outcome
Title Time to Intravenous (IV) Antipseudomonal Antibiotics
Hide Description 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.
Time Frame Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 85 189
Median (95% Confidence Interval)
Unit of Measure: Days
276
(217 to 316)
232
(179 to 288)
Time Frame Participants were monitored for AEs and SAEs during all on-treatment and off-treatment intervals. Participants could receive up to 9 courses of AZLI, with total time on study of up to 18 months. Events occurring during the 18-month period are reported.
Adverse Event Reporting Description A treatment-emergent AE was any physical or clinical worsening in symptoms or disease experienced by the participant at any time during the course of the study, whether or not the event was considered related to study participation or study procedures. An SAE was any adverse experience that resulted in death or hospitalization.
 
Arm/Group Title 75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Hide Arm/Group Description

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

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

All-Cause Mortality
75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Affected / at Risk (%) Affected / at Risk (%)
Total   38/85 (44.71%)   100/189 (52.91%) 
Blood and lymphatic system disorders     
Anaemia  0/85 (0.00%)  1/189 (0.53%) 
Cardiac disorders     
Cyanosis  0/85 (0.00%)  1/189 (0.53%) 
Tachycardia  0/85 (0.00%)  1/189 (0.53%) 
Gastrointestinal disorders     
Abdominal pain  4/85 (4.71%)  7/189 (3.70%) 
Abdominal pain lower  0/85 (0.00%)  2/189 (1.06%) 
Abdominal pain upper  1/85 (1.18%)  5/189 (2.65%) 
Abdominal tenderness  0/85 (0.00%)  2/189 (1.06%) 
Constipation  1/85 (1.18%)  4/189 (2.12%) 
Diarrhoea  0/85 (0.00%)  1/189 (0.53%) 
Distal intestinal obstruction syndrome  0/85 (0.00%)  1/189 (0.53%) 
Dyspepsia  1/85 (1.18%)  0/189 (0.00%) 
Gastrointestinal disorder  0/85 (0.00%)  1/189 (0.53%) 
Infrequent bowel movements  1/85 (1.18%)  0/189 (0.00%) 
Inguinal hernia  0/85 (0.00%)  1/189 (0.53%) 
Nausea  0/85 (0.00%)  2/189 (1.06%) 
Pancreatitis  1/85 (1.18%)  1/189 (0.53%) 
Vomiting  2/85 (2.35%)  5/189 (2.65%) 
General disorders     
Asthenia  1/85 (1.18%)  4/189 (2.12%) 
Exercise tolerance decreased  6/85 (7.06%)  19/189 (10.05%) 
Fatigue  4/85 (4.71%)  10/189 (5.29%) 
Lethargy  0/85 (0.00%)  3/189 (1.59%) 
Malaise  1/85 (1.18%)  2/189 (1.06%) 
Pain  1/85 (1.18%)  1/189 (0.53%) 
Pyrexia  6/85 (7.06%)  10/189 (5.29%) 
Hepatobiliary disorders     
Hepatitis acute  0/85 (0.00%)  1/189 (0.53%) 
Infections and infestations     
Staphylococcal infection  0/85 (0.00%)  1/189 (0.53%) 
Investigations     
Blood chloride decreased  0/85 (0.00%)  1/189 (0.53%) 
Blood creatinine increased  0/85 (0.00%)  2/189 (1.06%) 
Blood culture positive  0/85 (0.00%)  1/189 (0.53%) 
Blood potassium decreased  1/85 (1.18%)  0/189 (0.00%) 
Forced expiratory volume decreased  1/85 (1.18%)  3/189 (1.59%) 
Lipase increased  0/85 (0.00%)  1/189 (0.53%) 
Oxygen saturation decreased  3/85 (3.53%)  1/189 (0.53%) 
Pulmonary function test decreased  2/85 (2.35%)  25/189 (13.23%) 
Urine output decreased  0/85 (0.00%)  1/189 (0.53%) 
Weight decreased  1/85 (1.18%)  4/189 (2.12%) 
Metabolism and nutrition disorders     
Anorexia  0/85 (0.00%)  4/189 (2.12%) 
Decreased appetite  3/85 (3.53%)  11/189 (5.82%) 
Dehydration  0/85 (0.00%)  3/189 (1.59%) 
Electrolyte imbalance  0/85 (0.00%)  1/189 (0.53%) 
Hyperglycaemia  0/85 (0.00%)  1/189 (0.53%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1/85 (1.18%)  0/189 (0.00%) 
Back pain  2/85 (2.35%)  0/189 (0.00%) 
Joint swelling  1/85 (1.18%)  0/189 (0.00%) 
Musculoskeletal chest pain  0/85 (0.00%)  2/189 (1.06%) 
Nervous system disorders     
Dizziness  0/85 (0.00%)  2/189 (1.06%) 
Headache  2/85 (2.35%)  4/189 (2.12%) 
Vocal cord paralysis  0/85 (0.00%)  1/189 (0.53%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  0/85 (0.00%)  1/189 (0.53%) 
Renal and urinary disorders     
Fluid retention  0/85 (0.00%)  1/189 (0.53%) 
Nephrolithiasis  1/85 (1.18%)  0/189 (0.00%) 
Reproductive system and breast disorders     
Pelvic pain  0/85 (0.00%)  1/189 (0.53%) 
Uterine leiomyoma  0/85 (0.00%)  1/189 (0.53%) 
Respiratory, thoracic and mediastinal disorders     
Atelectasis  0/85 (0.00%)  1/189 (0.53%) 
Breath sounds decreased  0/85 (0.00%)  2/189 (1.06%) 
Bronchiectasis  0/85 (0.00%)  1/189 (0.53%) 
Bronchopneumonia  0/85 (0.00%)  1/189 (0.53%) 
Chest discomfort  3/85 (3.53%)  3/189 (1.59%) 
Cough  20/85 (23.53%)  58/189 (30.69%) 
Crackles lung  1/85 (1.18%)  7/189 (3.70%) 
Dyspnoea  11/85 (12.94%)  30/189 (15.87%) 
Dyspnoea exacerbated  1/85 (1.18%)  13/189 (6.88%) 
Dyspnoea exertional  0/85 (0.00%)  4/189 (2.12%) 
Haemoptysis  6/85 (7.06%)  18/189 (9.52%) 
Hypoxia  1/85 (1.18%)  5/189 (2.65%) 
Increased viscosity of bronchial secretion  1/85 (1.18%)  1/189 (0.53%) 
Lung infiltration  1/85 (1.18%)  2/189 (1.06%) 
Nasal congestion  0/85 (0.00%)  2/189 (1.06%) 
Non-cardiac chest pain  0/85 (0.00%)  4/189 (2.12%) 
Pharyngolaryngeal pain  1/85 (1.18%)  1/189 (0.53%) 
Pleuritic pain  0/85 (0.00%)  2/189 (1.06%) 
Pneumonia  1/85 (1.18%)  1/189 (0.53%) 
Pneumonia bacterial  0/85 (0.00%)  1/189 (0.53%) 
Pneumothorax  1/85 (1.18%)  0/189 (0.00%) 
Productive cough  12/85 (14.12%)  46/189 (24.34%) 
Rales  2/85 (2.35%)  0/189 (0.00%) 
Respiratory distress  1/85 (1.18%)  0/189 (0.00%) 
Respiratory tract congestion  3/85 (3.53%)  15/189 (7.94%) 
Respiratory tract infection  0/85 (0.00%)  1/189 (0.53%) 
Rhinorrhoea  0/85 (0.00%)  4/189 (2.12%) 
Rhonchi  1/85 (1.18%)  0/189 (0.00%) 
Sinus congestion  1/85 (1.18%)  2/189 (1.06%) 
Sputum discoloured  3/85 (3.53%)  5/189 (2.65%) 
Sputum purulent  1/85 (1.18%)  0/189 (0.00%) 
Tachypnoea  0/85 (0.00%)  1/189 (0.53%) 
Wheezing  1/85 (1.18%)  5/189 (2.65%) 
Skin and subcutaneous tissue disorders     
Rash  0/85 (0.00%)  1/189 (0.53%) 
Surgical and medical procedures     
Antibacterial prophylaxis  2/85 (2.35%)  5/189 (2.65%) 
Gastrostomy tube insertion  1/85 (1.18%)  0/189 (0.00%) 
Oxygen supplementation  1/85 (1.18%)  1/189 (0.53%) 
Vascular disorders     
Peripheral ischaemia  0/85 (0.00%)  1/189 (0.53%) 
1
Term from vocabulary, MedDRA 8.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
75 mg AZLI Two Times a Day (BID) 75 mg AZLI Three Times a Day (TID)
Affected / at Risk (%) Affected / at Risk (%)
Total   83/85 (97.65%)   185/189 (97.88%) 
Ear and labyrinth disorders     
Ear pain  5/85 (5.88%)  15/189 (7.94%) 
Gastrointestinal disorders     
Abdominal distension  4/85 (4.71%)  11/189 (5.82%) 
Abdominal pain  10/85 (11.76%)  20/189 (10.58%) 
Abdominal pain upper  12/85 (14.12%)  20/189 (10.58%) 
Constipation  8/85 (9.41%)  17/189 (8.99%) 
Diarrhoea  10/85 (11.76%)  30/189 (15.87%) 
Nausea  13/85 (15.29%)  40/189 (21.16%) 
Vomiting  18/85 (21.18%)  38/189 (20.11%) 
General disorders     
Asthenia  4/85 (4.71%)  24/189 (12.70%) 
Chills  7/85 (8.24%)  19/189 (10.05%) 
Exercise tolerance decreased  42/85 (49.41%)  104/189 (55.03%) 
Fatigue  31/85 (36.47%)  80/189 (42.33%) 
Pain  8/85 (9.41%)  17/189 (8.99%) 
Pyrexia  38/85 (44.71%)  83/189 (43.92%) 
Investigations     
Blood glucose increased  4/85 (4.71%)  15/189 (7.94%) 
Forced expiratory volume decreased  6/85 (7.06%)  11/189 (5.82%) 
Pulmonary function test decreased  10/85 (11.76%)  37/189 (19.58%) 
Weight decreased  13/85 (15.29%)  24/189 (12.70%) 
Metabolism and nutrition disorders     
Decreased appetite  25/85 (29.41%)  83/189 (43.92%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  12/85 (14.12%)  25/189 (13.23%) 
Back pain  11/85 (12.94%)  24/189 (12.70%) 
Chest wall pain  1/85 (1.18%)  12/189 (6.35%) 
Musculoskeletal chest pain  1/85 (1.18%)  12/189 (6.35%) 
Myalgia  7/85 (8.24%)  17/189 (8.99%) 
Pain in extremity  4/85 (4.71%)  15/189 (7.94%) 
Nervous system disorders     
Dizziness  4/85 (4.71%)  12/189 (6.35%) 
Headache  25/85 (29.41%)  61/189 (32.28%) 
Respiratory, thoracic and mediastinal disorders     
Breath sounds decreased  3/85 (3.53%)  11/189 (5.82%) 
Chest discomfort  19/85 (22.35%)  45/189 (23.81%) 
Cough  74/85 (87.06%)  166/189 (87.83%) 
Crackles lung  26/85 (30.59%)  37/189 (19.58%) 
Dysphonia  1/85 (1.18%)  16/189 (8.47%) 
Dyspnoea  20/85 (23.53%)  46/189 (24.34%) 
Dyspnoea exacerbated  6/85 (7.06%)  25/189 (13.23%) 
Dyspnoea exertional  7/85 (8.24%)  22/189 (11.64%) 
Epistaxis  9/85 (10.59%)  12/189 (6.35%) 
Haemoptysis  24/85 (28.24%)  59/189 (31.22%) 
Nasal congestion  33/85 (38.82%)  70/189 (37.04%) 
Nasal mucosal disorder  7/85 (8.24%)  10/189 (5.29%) 
Nasal oedema  9/85 (10.59%)  5/189 (2.65%) 
Nasal polyps  2/85 (2.35%)  10/189 (5.29%) 
Nasopharyngitis  7/85 (8.24%)  5/189 (2.65%) 
Non-cardiac chest pain  18/85 (21.18%)  33/189 (17.46%) 
Paranasal sinus hypersecretion  1/85 (1.18%)  14/189 (7.41%) 
Pharyngeal erythema  5/85 (5.88%)  8/189 (4.23%) 
Pharyngolaryngeal pain  41/85 (48.24%)  83/189 (43.92%) 
Postnasal drip  2/85 (2.35%)  20/189 (10.58%) 
Productive cough  56/85 (65.88%)  155/189 (82.01%) 
Rales  5/85 (5.88%)  6/189 (3.17%) 
Respiratory tract congestion  38/85 (44.71%)  90/189 (47.62%) 
Rhinitis  4/85 (4.71%)  18/189 (9.52%) 
Rhinorrhoea  23/85 (27.06%)  62/189 (32.80%) 
Rhonchi  6/85 (7.06%)  11/189 (5.82%) 
Sinus congestion  9/85 (10.59%)  41/189 (21.69%) 
Sinus headache  9/85 (10.59%)  30/189 (15.87%) 
Sneezing  3/85 (3.53%)  14/189 (7.41%) 
Sputum discoloured  1/85 (1.18%)  19/189 (10.05%) 
Wheezing  26/85 (30.59%)  50/189 (26.46%) 
Skin and subcutaneous tissue disorders     
Pruritus  1/85 (1.18%)  10/189 (5.29%) 
Rash  6/85 (7.06%)  18/189 (9.52%) 
1
Term from vocabulary, MedDRA 8.0
Descriptive statistics for all participants receiving 1 or more doses of AZLI were summarized for the safety, microbiology, and efficacy endpoints. No formal hypothesis tests were planned. Rates of AEs and SAEs are not adjusted for time on study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mark Bresnik, Director of Clinical Research
Organization: Gilead Sciences, Inc.
Phone: 650-522-5934
EMail: Mark.Bresnik@gilead.com
Layout table for additonal information
Responsible Party: Mark Bresnik, MD, Director, Clinical Research, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier: NCT00128492     History of Changes
Other Study ID Numbers: CP-AI-006
First Submitted: August 8, 2005
First Posted: August 10, 2005
Results First Submitted: June 3, 2010
Results First Posted: March 11, 2011
Last Update Posted: May 19, 2011