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Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

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ClinicalTrials.gov Identifier: NCT01059565
Recruitment Status : Completed
First Posted : February 1, 2010
Results First Posted : March 11, 2014
Last Update Posted : March 11, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Cystic Fibrosis
Burkholderia Infections
Interventions Drug: AZLI
Drug: Placebo
Enrollment 102
Recruitment Details Participants were enrolled at 34 sites in the United States and 1 site in Canada. The first participant was screened on 22 February 2010. The last participant observation was on 28 December 2010.
Pre-assignment Details 102 participants were screened and 101 were randomized. Of those participants randomized, 100 received at least one dose of study drug, and comprise the Safety Analysis Set and the Full Analysis Set.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description Aztreonam for inhalation solution (AZLI; 75 mg aztreonam/52.5 mg lysine monohydrate) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer. After the 24-week randomized phase, participants continued to receive AZLI during the open-label phase. Placebo to match AZLI (lactose and sodium chloride) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer. After the 24-week randomized phase, participants switched to AZLI during the open-label phase.
Period Title: 24-Week Randomized Phase
Started 49 52
Randomized and Treated 48 52
Completed 39 45
Not Completed 10 7
Reason Not Completed
Randomized but not treated             1             0
Adverse Event             5             0
Withdrawal by Subject             3             1
Lost to Follow-up             0             1
Noncompliance with Study Drug Regimen             1             5
Period Title: 24-Week Open-Label Phase
Started 39 45
Completed 34 42
Not Completed 5 3
Reason Not Completed
Adverse Event             2             0
Worsening health (physician decision)             1             1
Withdrawal by Subject             1             0
Subject noncompliance             1             0
Unable to clean device (hospitalization)             0             1
Pulmonologist/participant decision             0             1
Arm/Group Title AZLI Placebo Total
Hide Arm/Group Description Aztreonam for inhalation solution (AZLI; 75 mg aztreonam/52.5 mg lysine monohydrate) was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer. Placebo to match AZLI (lactose and sodium chloride) was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer. Total of all reporting groups
Overall Number of Baseline Participants 48 52 100
Hide Baseline Analysis Population Description
Full Analysis Set: participants were randomized and received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 52 participants 100 participants
28.0  (10.3) 24.7  (10.0) 26.3  (10.2)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 52 participants 100 participants
≥ 6 to ≤ 12 years 3 3 6
> 12 to < 18 years 3 8 11
≥ 18 years 42 41 83
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 52 participants 100 participants
Female
22
  45.8%
17
  32.7%
39
  39.0%
Male
26
  54.2%
35
  67.3%
61
  61.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 52 participants 100 participants
Hispanic or Latino
0
   0.0%
1
   1.9%
1
   1.0%
Not Hispanic or Latino
48
 100.0%
51
  98.1%
99
  99.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 52 participants 100 participants
Black or African Heritage 1 2 3
White 46 50 96
Other 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 52 participants 100 participants
United States 45 49 94
Canada 3 3 6
Forced expiratory volume in 1 second (FEV1) percent predicted   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of FEV1 % predicted
Number Analyzed 48 participants 52 participants 100 participants
60.67  (21.71) 52.59  (23.71) 56.47  (23.02)
[1]
Measure Description: FEV1 % predicted is defined as FEV1 % of the patient divided by the average FEV1 % in the population for any person of similar age, sex and body composition.
FEV1   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 48 participants 52 participants 100 participants
2.13  (0.93) 1.93  (0.96) 2.02  (0.95)
[1]
Measure Description: FEV1 is defined as the maximal volume of air that can be exhaled in 1 second.
Forced vital capacity (FVC)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 48 participants 52 participants 100 participants
3.23  (1.18) 2.99  (1.14) 3.11  (1.16)
[1]
Measure Description: FVC is defined as the volume of air that can forcibly be blown out after taking a full breath.
Forced expiratory flow 25% to 75% (FEF25-75)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters per second
Number Analyzed 48 participants 52 participants 100 participants
1.33  (0.95) 1.31  (1.22) 1.32  (1.09)
[1]
Measure Description: FEF25-75 is defined as the forced expiratory flow from 25% to 75% of the FVC.
Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 48 participants 52 participants 100 participants
58.3  (21.4) 59.0  (17.6) 58.6  (19.4)
[1]
Measure Description: Respiratory symptoms (e.g., coughing, congestion, wheezing) were assessed with the CFQ-R Respiratory Symptoms Scale (RSS). The range of scores (units) is 0 to 100 with higher scores indicating fewer symptoms.
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 48 participants 52 participants 100 participants
21.9  (4.5) 20.7  (3.2) 21.3  (3.9)
Burkholderia spp colony-forming units (CFU) in sputum   [1] 
Mean (Standard Deviation)
Unit of measure:  Log_10 CFU per gram
Number Analyzed 48 participants 52 participants 100 participants
6.39  (2.47) 6.41  (2.52) 6.40  (2.48)
[1]
Measure Description: Participants in the Full Analysis Set with evaluable assessments for Burkholderia spp. CFU in sputum at baseline were analyzed, which included 30 in the AZLI group, 32 in the placebo group, and 62 total.
1.Primary Outcome
Title AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24
Hide Description The relative change (AUCave) in FEV1 % predicted from baseline to Week 24 was analyzed. FEV1 % predicted is defined as FEV1 % of the patient divided by the average FEV1 % in the population for any person of similar age, sex and body composition. AUCave is the calculated area under the curve corrected for baseline and adjusted by the number of days on study through Week 24.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 48 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change in FEV1% predicted
0.16  (1.50) -0.75  (1.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments

The primary analysis was a test for superiority. Null hypothesis was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.

A sample size of 50 participants per group provided at least 80% power to detect an 8.5% difference in mean AUCave of relative change from baseline in FEV1 % predicted through Week 24 using a two-sided 0.05-level test, assuming a common standard deviation of 15.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.663
Comments

To correct for multiplicity, a family alpha spending rule was used to control the type 1 error rate of alpha=0.05.

A gate-keeping procedure to control family-wise Type 1 error was established a priori for primary and key secondary endpoints.

Method ANCOVA
Comments Baseline was included as a covariate in this model.
Method of Estimation Estimation Parameter Difference in least squares mean (LSM)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
-3.24 to 5.06
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events
Hide Description The total number of systemic and/or inhaled antibiotic courses for respiratory events from baseline to Week 24 was analyzed. A single antibiotic course may represent the use of multiple antibiotics.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 48 52
Measure Type: Number
Unit of Measure: antibiotic treatment courses
54 73
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments The primary analysis was a test for superiority. Null hypothesis was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4158
Comments To correct for multiplicity, a family alpha spending rule was used to control the type 1 error rate of alpha=0.05.
Method Negative binomial regression
Comments The negative binomial regression model included an offset parameter which accounted for potential differing study durations due to discontinuations.
3.Secondary Outcome
Title AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24
Hide Description

The change (AUCave) in CFQ-R RSS scores from baseline to Week 24 was analyzed.

The range of scores (units) within the RSS domain is 0 to 100 with higher scores indicating fewer symptoms.

Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 45 52
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.97  (1.70) 2.79  (1.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.939
Comments To correct for multiplicity, a family alpha spending rule was used to control the type 1 error rate of alpha=0.05.
Method ANCOVA
Comments The AUCs of changes from baseline were compared between treatment groups using ANCOVA methods with baseline value as a covariate.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-4.43 to 1.78
Estimation Comments [Not Specified]
4.Secondary Outcome
Title AUCave of Relative Change From Baseline to Week 24 in FEV1
Hide Description The relative change (AUCave) from baseline to Week 24 in mean (SE) FEV1 was analyzed. FEV1 is defined as the maximal volume of air that can be exhaled in 1 second.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 47 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change in FEV1 (liters)
0.36  (1.49) -0.41  (1.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.711
Comments [Not Specified]
Method ANCOVA
Comments The AUCs of changes from baseline were compared between treatment groups using ANCOVA methods with baseline value as a covariate.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
-3.33 to 4.86
Estimation Comments [Not Specified]
5.Secondary Outcome
Title AUCave of Relative Change From Baseline to Week 24 in FVC
Hide Description The relative change (AUCave) from baseline to Week 24 in mean (SE) FVC was analyzed. FVC is defined as the volume of air that can forcibly be blown out after taking a full breath.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 47 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change in FVC (liters)
0.77  (1.42) 0.17  (1.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.762
Comments [Not Specified]
Method ANCOVA
Comments The AUCs of changes from baseline were compared between treatment groups using ANCOVA methods with baseline value as a covariate.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
-3.30 to 4.49
Estimation Comments [Not Specified]
6.Secondary Outcome
Title AUCave of Relative Change From Baseline to Week 24 in FEF25-75
Hide Description The relative change (AUCave) from baseline to Week 24 in mean (SE) FEF25-75 was analyzed. FEF25-75 is defined as the forced expiratory flow from 25% to 75% of the FVC.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 47 52
Least Squares Mean (Standard Error)
Unit of Measure: percent change in FEF25-75 (liters/sec)
1.40  (2.37) -0.55  (2.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.553
Comments [Not Specified]
Method ANCOVA
Comments The AUCs of changes from baseline were compared between treatment groups using ANCOVA methods with baseline value as a covariate.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
-4.54 to 8.44
Estimation Comments [Not Specified]
7.Secondary Outcome
Title AUCave of the Change From Baseline to Week 24 in Physical Functioning Score as Assessed by the CFQ-R
Hide Description

The change (AUCave) from baseline to Week 24 in the physical functioning score as assessed by the CFQ-R was analyzed.

The range of scores (units) in the CFQ-R physical functioning domain is 0 to 100 with higher scores indicating better QOL.

Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 46 52
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.06  (1.57) -1.93  (1.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.170
Comments [Not Specified]
Method ANCOVA
Comments Baseline was included as a covariate in this model.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 2.99
Confidence Interval (2-Sided) 95%
-1.20 to 7.28
Estimation Comments [Not Specified]
8.Secondary Outcome
Title AUCave of the Change From Baseline to Week 24 in Weight Score as Assessed by the CFQ-R
Hide Description

The change (AUCave) from baseline to Week 24 in the weight score as assessed by the CFQ-R was analyzed.

The range of scores (units) in the CFQ-R weight domain is 0 to 100 with higher scores indicating better QOL.

Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 44 47
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.54  (2.90) 3.11  (2.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.528
Comments [Not Specified]
Method ANCOVA
Comments Baseline was included as a covariate in this model.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value -2.57
Confidence Interval (2-Sided) 95%
-10.62 to 5.49
Estimation Comments [Not Specified]
9.Secondary Outcome
Title AUCave of the Change From Baseline to Week 24 in Treatment Burden Score as Assessed by the CFQ-R
Hide Description

The change (AUCave) from baseline to Week 24 in the treatment burden score as assessed by the CFQ-R was analyzed.

The range of scores (units) in the CFQ-R treatment burden domain is 0 to 100 with higher scores indicating better QOL.

Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 46 52
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.73  (1.73) -6.35  (1.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.132
Comments [Not Specified]
Method ANCOVA
Comments Baseline was included as a covariate in this model.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 3.62
Confidence Interval (2-Sided) 95%
-1.11 to 8.34
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in BMI From Baseline to Week 24
Hide Description The change in BMI from baseline to Week 24 was analyzed.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 39 45
Least Squares Mean (Standard Error)
Unit of Measure: kg/m^2
0.34  (0.16) 0.21  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.531
Comments [Not Specified]
Method Mixed Models Analysis
Comments P-value was based on a Mixed-Effect Model Repeated Measure model that included terms for treatment, visit, baseline, and treatment/visit interaction.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.29 to 0.56
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in Burkholderia Spp. CFU in Sputum From Baseline to Week 24
Hide Description The change in Burkholderia spp. CFU in sputum from baseline to Week 24 was analyzed.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available change data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 15 20
Least Squares Mean (Standard Error)
Unit of Measure: log_10 CFU per gram of sputum
1.41  (0.58) 0.48  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.232
Comments [Not Specified]
Method ANCOVA
Comments Baseline was included as a covariate in this model.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
-0.62 to 2.48
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Days Participants Used Antibiotics
Hide Description The percentage of days participants used antibiotics from baseline to Week 24 was analyzed. Antibiotics ongoing at baseline or started on or after first dose date were included in the analysis. A single antibiotic course could represent the use of multiple antibiotics. Days of antibiotic use included unique days.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 47 52
Mean (Standard Deviation)
Unit of Measure: percentage of days
44.4  (35.2) 56.3  (34.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.103
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
13.Secondary Outcome
Title Percent of Days Hospitalized
Hide Description The percentage of days hospitalized from baseline to Week 24 was analyzed.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 48 52
Mean (Standard Deviation)
Unit of Measure: percentage of days
4.9  (10.3) 4.8  (8.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.646
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Missed School or Work Days
Hide Description The percentage of days participants missed school or work from baseline to Week 24 was analyzed.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title AZLI Placebo
Hide Arm/Group Description:
AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Placebo to match AZLI was administered three times a day, with at least 4 hours between doses, for up 48 weeks using the investigational nebulizer.
Overall Number of Participants Analyzed 32 40
Mean (Standard Deviation)
Unit of Measure: percentage of days
1.9  (3.3) 4.7  (7.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZLI, Placebo
Comments Null hypothesis was that there was no difference between the AZLI and placebo treatment groups versus the alternative hypothesis that there was a difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.284
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Baseline to Week 24
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZLI Placebo AZLI/AZLI Placebo/AZLI
Hide Arm/Group Description For the reporting of Adverse Events, this group includes participants who were randomized to receive AZLI at baseline, and were analyzed from Baseline to Week 24. For the reporting of Adverse Events, this group includes participants who were randomized to receive placebo at baseline, and were analyzed from Baseline to Week 24. For the reporting of Adverse Events, this group includes participants who were randomized to receive AZLI at baseline and continued to receive an up to an additional 24 weeks of AZLI treatment during the open-label phase, and were analyzed from Week 24 to Week 48. For the reporting of Adverse Events, this group includes participants who were randomized to receive placebo at baseline and switched AZLI for up to 24 weeks of treatment during the open-label phase, and were analyzed from Week 24 to Week 48.
All-Cause Mortality
AZLI Placebo AZLI/AZLI Placebo/AZLI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AZLI Placebo AZLI/AZLI Placebo/AZLI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/48 (35.42%)   21/52 (40.38%)   19/39 (48.72%)   24/45 (53.33%) 
Gastrointestinal disorders         
Abdominal pain  1  0/48 (0.00%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Constipation  1  0/48 (0.00%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Pancreatitis chronic  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Small intestinal obstruction  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
General disorders         
Chest pain  1  0/48 (0.00%)  1/52 (1.92%)  0/39 (0.00%)  1/45 (2.22%) 
Non-cardiac chest pain  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Cholethiasis  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Infections and infestations         
Pneumonia bacterial  1  0/48 (0.00%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Infective pulmonary exacerbation of cycstic fibrosis  1  10/48 (20.83%)  6/52 (11.54%)  8/39 (20.51%)  11/45 (24.44%) 
Pneumonia  1  0/48 (0.00%)  1/52 (1.92%)  2/39 (5.13%)  0/45 (0.00%) 
Sepsis  1  1/48 (2.08%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Sinusitis  1  0/48 (0.00%)  1/52 (1.92%)  1/39 (2.56%)  0/45 (0.00%) 
Gastroenteritis  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Influenza  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Pneumonia staphylococcal  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Acute sinusitis  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Viral infection  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  1/45 (2.22%) 
Injury, poisoning and procedural complications         
Procedural site reaction  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Investigations         
Pulmonary function test decreased  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Metabolism and nutrition disorders         
Dehydration  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthritis reactive  1  0/48 (0.00%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Arthralgia  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Psychiatric disorders         
Mental status changes  1  1/48 (2.08%)  0/52 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Reproductive system and breast disorders         
Haematspermia  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  1/48 (2.08%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Haemoptysis  1  1/48 (2.08%)  0/52 (0.00%)  2/39 (5.13%)  2/45 (4.44%) 
Pleuritic pain  1  0/48 (0.00%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Sinus disorder  1  1/48 (2.08%)  0/52 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Pneumothorax  1  1/48 (2.08%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Respiratory failure  1  1/48 (2.08%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Lung disorder  1  7/48 (14.58%)  14/52 (26.92%)  9/39 (23.08%)  9/45 (20.00%) 
Respiratory arrest  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Asthma  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Bronchospasm  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Epistaxis  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Pulmonary embolism  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Vascular disorders         
Deep vein thrombosis  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Superior vena cava syndrome  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZLI Placebo AZLI/AZLI Placebo/AZLI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   46/48 (95.83%)   46/52 (88.46%)   39/39 (100.00%)   44/45 (97.78%) 
Blood and lymphatic system disorders         
Lymphadenopathy  1  0/48 (0.00%)  0/52 (0.00%)  3/39 (7.69%)  0/45 (0.00%) 
Cardiac disorders         
Tachycardia  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  2/45 (4.44%) 
Ear and labyrinth disorders         
Ear discomfort  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Ear pain  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Tinnitus  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  1/45 (2.22%) 
Gastrointestinal disorders         
Abdominal pain  1  3/48 (6.25%)  3/52 (5.77%)  4/39 (10.26%)  6/45 (13.33%) 
Abdominal pain upper  1  4/48 (8.33%)  1/52 (1.92%)  0/39 (0.00%)  0/45 (0.00%) 
Constipation  1  3/48 (6.25%)  3/52 (5.77%)  1/39 (2.56%)  5/45 (11.11%) 
Diarrhoea  1  6/48 (12.50%)  6/52 (11.54%)  4/39 (10.26%)  6/45 (13.33%) 
Nausea  1  11/48 (22.92%)  10/52 (19.23%)  7/39 (17.95%)  7/45 (15.56%) 
Vomiting  1  7/48 (14.58%)  5/52 (9.62%)  4/39 (10.26%)  4/45 (8.89%) 
Post-tussive vomiting  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  1/45 (2.22%) 
Abdominal distension  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  1/45 (2.22%) 
General disorders         
Chest discomfort  1  13/48 (27.08%)  8/52 (15.38%)  6/39 (15.38%)  9/45 (20.00%) 
Chest pain  1  7/48 (14.58%)  1/52 (1.92%)  13/39 (33.33%)  10/45 (22.22%) 
Chills  1  6/48 (12.50%)  2/52 (3.85%)  8/39 (20.51%)  3/45 (6.67%) 
Exercise tolerance decreased  1  5/48 (10.42%)  1/52 (1.92%)  1/39 (2.56%)  3/45 (6.67%) 
Fatigue  1  10/48 (20.83%)  11/52 (21.15%)  14/39 (35.90%)  12/45 (26.67%) 
Non-cardiac chest pain  1  3/48 (6.25%)  3/52 (5.77%)  3/39 (7.69%)  2/45 (4.44%) 
Pain  1  6/48 (12.50%)  2/52 (3.85%)  3/39 (7.69%)  5/45 (11.11%) 
Pyrexia  1  19/48 (39.58%)  17/52 (32.69%)  16/39 (41.03%)  19/45 (42.22%) 
Asthenia  1  4/48 (8.33%)  3/52 (5.77%)  2/39 (5.13%)  4/45 (8.89%) 
Malaise  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  3/45 (6.67%) 
Oedema peripheral  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Infections and infestations         
Rhinitis  1  0/48 (0.00%)  3/52 (5.77%)  0/39 (0.00%)  0/45 (0.00%) 
Sinusitis  1  1/48 (2.08%)  4/52 (7.69%)  4/39 (10.26%)  5/45 (11.11%) 
Candidiasis  1  0/48 (0.00%)  0/52 (0.00%)  0/39 (0.00%)  3/45 (6.67%) 
Injury, poisoning and procedural complications         
Procedural pain  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  5/45 (11.11%) 
Investigations         
Forced expiratory volume decreased  1  2/48 (4.17%)  3/52 (5.77%)  5/39 (12.82%)  1/45 (2.22%) 
Pulmonary function test decreased  1  5/48 (10.42%)  8/52 (15.38%)  3/39 (7.69%)  9/45 (20.00%) 
Weight decreased  1  3/48 (6.25%)  3/52 (5.77%)  4/39 (10.26%)  7/45 (15.56%) 
Breath sounds abmormal  1  0/48 (0.00%)  0/52 (0.00%)  4/39 (10.26%)  2/45 (4.44%) 
Vitamin D decreased  1  0/48 (0.00%)  0/52 (0.00%)  4/39 (10.26%)  2/45 (4.44%) 
Oxygen saturation decreased  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  3/45 (6.67%) 
Metabolism and nutrition disorders         
Decreased appetite  1  8/48 (16.67%)  6/52 (11.54%)  8/39 (20.51%)  7/45 (15.56%) 
Hyperglycaemia  1  3/48 (6.25%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Malnutrition  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  1/45 (2.22%) 
Metabolic acidosis  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  3/48 (6.25%)  6/52 (11.54%)  4/39 (10.26%)  4/45 (8.89%) 
Back pain  1  4/48 (8.33%)  6/52 (11.54%)  3/39 (7.69%)  3/45 (6.67%) 
Pain in extremity  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  3/45 (6.67%) 
Myalgia  1  0/48 (0.00%)  0/52 (0.00%)  4/39 (10.26%)  2/45 (4.44%) 
Nervous system disorders         
Dizziness  1  5/48 (10.42%)  3/52 (5.77%)  0/39 (0.00%)  0/45 (0.00%) 
Headache  1  6/48 (12.50%)  7/52 (13.46%)  8/39 (20.51%)  6/45 (13.33%) 
Sinus headache  1  8/48 (16.67%)  3/52 (5.77%)  9/39 (23.08%)  1/45 (2.22%) 
Psychiatric disorders         
Insomnia  1  4/48 (8.33%)  1/52 (1.92%)  4/39 (10.26%)  5/45 (11.11%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  34/48 (70.83%)  32/52 (61.54%)  31/39 (79.49%)  34/45 (75.56%) 
Dyspnoea  1  14/48 (29.17%)  15/52 (28.85%)  17/39 (43.59%)  21/45 (46.67%) 
Haemoptysis  1  13/48 (27.08%)  17/52 (32.69%)  11/39 (28.21%)  8/45 (17.78%) 
Increased viscosity of bronchial secretion  1  4/48 (8.33%)  2/52 (3.85%)  2/39 (5.13%)  1/45 (2.22%) 
Nasal congestion  1  12/48 (25.00%)  14/52 (26.92%)  16/39 (41.03%)  14/45 (31.11%) 
Oropharyngeal pain  1  15/48 (31.25%)  11/52 (21.15%)  15/39 (38.46%)  15/45 (33.33%) 
Paranasal sinus hypersectretion  1  2/48 (4.17%)  3/52 (5.77%)  2/39 (5.13%)  2/45 (4.44%) 
Pleuritic pain  1  3/48 (6.25%)  0/52 (0.00%)  3/39 (7.69%)  1/45 (2.22%) 
Productive cough  1  4/48 (8.33%)  1/52 (1.92%)  5/39 (12.82%)  3/45 (6.67%) 
Rales  1  5/48 (10.42%)  6/52 (11.54%)  7/39 (17.95%)  6/45 (13.33%) 
Respiratory tract congestion  1  7/48 (14.58%)  14/52 (26.92%)  13/39 (33.33%)  11/45 (24.44%) 
Rhinorrheoa  1  8/48 (16.67%)  6/52 (11.54%)  10/39 (25.64%)  9/45 (20.00%) 
Sinus congestion  1  8/48 (16.67%)  5/52 (9.62%)  12/39 (30.77%)  3/45 (6.67%) 
Sputum discoloured  1  1/48 (2.08%)  3/52 (5.77%)  4/39 (10.26%)  4/45 (8.89%) 
Sputum increased  1  23/48 (47.92%)  20/52 (38.46%)  19/39 (48.72%)  14/45 (31.11%) 
Upper airway cough syndrome  1  4/48 (8.33%)  6/52 (11.54%)  2/39 (5.13%)  2/45 (4.44%) 
Wheezing  1  10/48 (20.83%)  3/52 (5.77%)  8/39 (20.51%)  6/45 (13.33%) 
Upper respiratory tract congestion  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Dyspnoea exertional  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  1/45 (2.22%) 
Epistaxis  1  0/48 (0.00%)  0/52 (0.00%)  3/39 (7.69%)  2/45 (4.44%) 
Pharyngeal erythema  1  0/48 (0.00%)  0/52 (0.00%)  4/39 (10.26%)  1/45 (2.22%) 
Hypoxia  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  1/45 (2.22%) 
Painful respiration  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Dysphonia  1  0/48 (0.00%)  0/52 (0.00%)  1/39 (2.56%)  3/45 (6.67%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  3/48 (6.25%)  0/52 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Pruritus  1  1/48 (2.08%)  3/52 (5.77%)  0/39 (0.00%)  3/45 (6.67%) 
Rash  1  0/48 (0.00%)  0/52 (0.00%)  4/39 (10.26%)  4/45 (8.89%) 
Night sweats  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  2/45 (4.44%) 
Swelling face  1  0/48 (0.00%)  0/52 (0.00%)  2/39 (5.13%)  0/45 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01059565     History of Changes
Other Study ID Numbers: GS-US-205-0127
First Submitted: January 28, 2010
First Posted: February 1, 2010
Results First Submitted: March 8, 2013
Results First Posted: March 11, 2014
Last Update Posted: March 11, 2014