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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01059565
First received: January 28, 2010
Last updated: February 7, 2014
Last verified: February 2014
Results First Received: March 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Cystic Fibrosis
Burkholderia Infections
Interventions: Drug: AZLI
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
AZLI 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 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.

Participant Flow for 2 periods

Period 1:   24-Week Randomized Phase
    AZLI     Placebo  
STARTED     49     52  
Randomized and Treated     48     52  
COMPLETED     39     45  
NOT COMPLETED     10     7  
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 2:   24-Week Open-Label Phase
    AZLI     Placebo  
STARTED     39     45  
COMPLETED     34     42  
NOT COMPLETED     5     3  
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  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set: participants were randomized and received at least one dose of study drug.

Reporting Groups
  Description
AZLI 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 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 Total of all reporting groups

Baseline Measures
    AZLI     Placebo     Total  
Number of Participants  
[units: participants]
  48     52     100  
Age  
[units: years]
Mean ± Standard Deviation
  28.0  ± 10.3     24.7  ± 10.0     26.3  ± 10.2  
Age, Customized  
[units: participants]
     
≥ 6 to ≤ 12 years     3     3     6  
> 12 to < 18 years     3     8     11  
≥ 18 years     42     41     83  
Gender  
[units: participants]
     
Female     22     17     39  
Male     26     35     61  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     0     1     1  
Not Hispanic or Latino     48     51     99  
Unknown or Not Reported     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
Black or African Heritage     1     2     3  
White     46     50     96  
Other     1     0     1  
Region of Enrollment  
[units: participants]
     
United States     45     49     94  
Canada     3     3     6  
Forced expiratory volume in 1 second (FEV1) percent predicted [1]
[units: percentage of FEV1 % predicted]
Mean ± Standard Deviation
  60.67  ± 21.71     52.59  ± 23.71     56.47  ± 23.02  
FEV1 [2]
[units: liters]
Mean ± Standard Deviation
  2.13  ± 0.93     1.93  ± 0.96     2.02  ± 0.95  
Forced vital capacity (FVC) [3]
[units: liters]
Mean ± Standard Deviation
  3.23  ± 1.18     2.99  ± 1.14     3.11  ± 1.16  
Forced expiratory flow 25% to 75% (FEF25-75) [4]
[units: liters per second]
Mean ± Standard Deviation
  1.33  ± 0.95     1.31  ± 1.22     1.32  ± 1.09  
Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score [5]
[units: units on a scale]
Mean ± Standard Deviation
  58.3  ± 21.4     59.0  ± 17.6     58.6  ± 19.4  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  21.9  ± 4.5     20.7  ± 3.2     21.3  ± 3.9  
Burkholderia spp colony-forming units (CFU) in sputum [6]
[units: log_10 CFU per gram]
Mean ± Standard Deviation
  6.39  ± 2.47     6.41  ± 2.52     6.40  ± 2.48  
[1] 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.
[2] FEV1 is defined as the maximal volume of air that can be exhaled in 1 second.
[3] FVC is defined as the volume of air that can forcibly be blown out after taking a full breath.
[4] FEF25-75 is defined as the forced expiratory flow from 25% to 75% of the FVC.
[5] 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.
[6] 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.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24   [ Time Frame: Baseline to Week 24 ]

2.  Secondary:   Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events   [ Time Frame: Baseline to Week 24 ]

3.  Secondary:   AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24   [ Time Frame: Baseline to Week 24 ]

4.  Secondary:   AUCave of Relative Change From Baseline to Week 24 in FEV1   [ Time Frame: Baseline to Week 24 ]

5.  Secondary:   AUCave of Relative Change From Baseline to Week 24 in FVC   [ Time Frame: Baseline to Week 24 ]

6.  Secondary:   AUCave of Relative Change From Baseline to Week 24 in FEF25-75   [ Time Frame: Baseline to Week 24 ]

7.  Secondary:   AUCave of the Change From Baseline to Week 24 in Physical Functioning Score as Assessed by the CFQ-R   [ Time Frame: Baseline to Week 24 ]

8.  Secondary:   AUCave of the Change From Baseline to Week 24 in Weight Score as Assessed by the CFQ-R   [ Time Frame: Baseline to Week 24 ]

9.  Secondary:   AUCave of the Change From Baseline to Week 24 in Treatment Burden Score as Assessed by the CFQ-R   [ Time Frame: Baseline to Week 24 ]

10.  Secondary:   Change in BMI From Baseline to Week 24   [ Time Frame: Baseline to Week 24 ]

11.  Secondary:   Change in Burkholderia Spp. CFU in Sputum From Baseline to Week 24   [ Time Frame: Baseline to Week 24 ]

12.  Secondary:   Percentage of Days Participants Used Antibiotics   [ Time Frame: Baseline to Week 24 ]

13.  Secondary:   Percent of Days Hospitalized   [ Time Frame: Baseline to Week 24 ]

14.  Secondary:   Percentage of Missed School or Work Days   [ Time Frame: Baseline to Week 24 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


No publications provided


Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01059565     History of Changes
Other Study ID Numbers: GS-US-205-0127
Study First Received: January 28, 2010
Results First Received: March 8, 2013
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration