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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trial to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects With Cystic Fibrosis (CF) and

Brief Summary:

The purpose of this research study was to determine if an experimental drug called Aztreonam for Inhalation Solution (AZLI) was safe and effective to treat Burkholderia lung infections in patients with cystic fibrosis (CF).

Spirometry was used to assess pulmonary function, and the revised Cystic Fibrosis Questionnaire (CFQ-R) was used to assess quality of life. The CFQ-R is a validated, patient-reported outcome tool used to measure health-related quality of life for children and adults with CF.

The study consisted of a 24-week randomized phase, and a 24-week open-label phase. Primary and secondary efficacy analyses were conducted for the 24-week randomized phase only. Safety data were collected for both the randomized and open-label phases.


Detailed Summary:
Sponsor: Gilead Sciences

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

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.


Original Primary Outcome: Change from baseline in FEV1 percent predicted as measured by the AUCave through week 24. [ Time Frame: 24 weeks ]

Current Secondary Outcome:

  • Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events [ Time Frame: Baseline to Week 24 ]
    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.
  • AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]

    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.

  • AUCave of Relative Change From Baseline to Week 24 in FEV1 [ Time Frame: Baseline to Week 24 ]
    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.
  • AUCave of Relative Change From Baseline to Week 24 in FVC [ Time Frame: Baseline to Week 24 ]
    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.
  • AUCave of Relative Change From Baseline to Week 24 in FEF25-75 [ Time Frame: Baseline to Week 24 ]
    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.
  • 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 ]

    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.

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

    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.

  • 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 ]

    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.

  • Change in BMI From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
    The change in BMI from baseline to Week 24 was analyzed.
  • Change in Burkholderia Spp. CFU in Sputum From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
    The change in Burkholderia spp. CFU in sputum from baseline to Week 24 was analyzed.
  • Percentage of Days Participants Used Antibiotics [ Time Frame: Baseline to Week 24 ]
    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.
  • Percent of Days Hospitalized [ Time Frame: Baseline to Week 24 ]
    The percentage of days hospitalized from baseline to Week 24 was analyzed.
  • Percentage of Missed School or Work Days [ Time Frame: Baseline to Week 24 ]
    The percentage of days participants missed school or work from baseline to Week 24 was analyzed.


Original Secondary Outcome: AUCave of relative change from baseline in FEV1, FVC, and FEF25 to 75 percent through week 24. [ Time Frame: 24 weeks ]

Information By: Gilead Sciences

Dates:
Date Received: January 28, 2010
Date Started: February 2010
Date Completion:
Last Updated: February 7, 2014
Last Verified: February 2014