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

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00128492
First received: August 8, 2005
Last updated: May 17, 2011
Last verified: May 2011
Results First Received: June 3, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Intervention: Drug: AZLI 75 mg two times a day (BID)/ three times a day (TID)

  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
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
75 mg AZLI Two Times a Day (BID)

Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy.

BID = twice daily

75 mg AZLI Three Times a Day (TID)

Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy.

TID = three times daily


Participant Flow:   Overall Study
    75 mg AZLI Two Times a Day (BID)     75 mg AZLI Three Times a Day (TID)  
STARTED     85     189  
COMPLETED     65     130  
NOT COMPLETED     20     59  
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  



  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.
No text entered.

Reporting Groups
  Description
75 mg AZLI Two Times a Day (BID)

Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy.

BID = twice daily

75 mg AZLI Three Times a Day (TID)

Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy.

TID = three times daily

Total Total of all reporting groups

Baseline Measures
    75 mg AZLI Two Times a Day (BID)     75 mg AZLI Three Times a Day (TID)     Total  
Number of Participants  
[units: participants]
  85     189     274  
Age  
[units: participants]
     
<=18 years     19     36     55  
Between 18 and 65 years     65     151     216  
>=65 years     1     2     3  
Age  
[units: years]
Mean ± Standard Deviation
  27.3  ± 11.4     29.0  ± 13.0     28.5  ± 12.5  
Gender  
[units: participants]
     
Female     34     89     123  
Male     51     100     151  
Region of Enrollment  
[units: 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]
[units: participants]
     
Aztreonam MIC > 8 µg/mL     30     72     102  
Aztreonam MIC < or = 8 µg/mL     46     99     145  
Unknown     9     18     27  
Disease severity as defined by FEV1 percent predicted category [2]
[units: Participants]
     
FEV1 > 50% predicted     49     114     163  
FEV1 ≤ 50% predicted     36     74     110  
Unknown     0     1     1  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  21.30  ± 3.25     21.44  ± 3.96     21.40  ± 3.75  
Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS) [3]
[units: Units on a scale]
Mean ± Standard Deviation
  65.410  ± 16.896     60.332  ± 18.497     61.895  ± 18.141  
Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted [4]
[units: Percent]
Mean ± Standard Deviation
  56.711  ± 17.505     55.071  ± 15.428     55.582  ± 16.089  
Log10 Pseudomonas aeruginosa (PA) Colony-Forming Units (CFUs) in Sputum  
[units: log10 CFUs/g]
Mean ± Standard Deviation
  5.71  ± 2.249     6.16  ± 1.894     6.02  ± 2.014  
Weight  
[units: kg]
Mean ± Standard Deviation
  59.52  ± 13.28     59.28  ± 15.81     59.36  ± 15.05  
[1] Number of partipipants with an MIC of aztreonam ≤ 8 µg/mL or >8 µg/mL for PA are summarized.
[2] 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.
[3] CFQ-R RSS scale range 0-100, with higher scores indicating fewer CF symptoms.
[4] FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Reporting Adverse Events (AEs)   [ Time Frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug ]

2.  Primary:   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   [ Time Frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug ]

3.  Primary:   Change in Heart Rate (HR)   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) ]

4.  Primary:   Change in Systolic and Diastolic Blood Pressure (BP)   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) ]

5.  Primary:   Change in Temperature   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) ]

6.  Primary:   Change in Respiratory Rate (RR)   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) ]

7.  Primary:   Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets   [ Time Frame: Baseline and end of Course 9 (Week 68) ]

8.  Primary:   Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

9.  Primary:   Serum Hematology - Number of Red Blood Cells (RBC)   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

10.  Primary:   Serum Hematology - Hematocrit   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

11.  Primary:   Serum Hematology - Hemoglobin   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

12.  Primary:   Serum Hematology - Mean Corpuscular Volume (MCV)   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

13.  Primary:   Serum Hematology - Mean Corpuscular Hemoglobin (MCH)   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

14.  Primary:   Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

15.  Primary:   Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

16.  Primary:   Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

17.  Primary:   Serum Chemistry - Concentration of Chloride, Potassium, and Sodium   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

18.  Primary:   Serum Chemistry - Concentration of Total Protein   [ Time Frame: Baseline and end of treatment Course 9 (Week 68) ]

19.  Secondary:   Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum   [ Time Frame: Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) ]

20.  Secondary:   Number of Participants With Other Pathogens   [ Time Frame: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72) ]

21.  Secondary:   Minimum Inhibitory Concentration (MIC) of Aztreonam   [ Time Frame: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72) ]

22.  Secondary:   Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75)   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) ]

23.  Secondary:   Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS)   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) ]

24.  Secondary:   Time to First Hospitalization Due to a Respiratory Event   [ Time Frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug ]

25.  Secondary:   Change in Body Weight   [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) ]

26.  Secondary:   Missed School/Work Days Due to CF Symptoms   [ Time Frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug ]

27.  Secondary:   Time to Intravenous (IV) Antipseudomonal Antibiotics   [ Time Frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
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.  


Results Point of Contact:  
Name/Title: Mark Bresnik, Director of Clinical Research
Organization: Gilead Sciences, Inc.
phone: 650-522-5934
e-mail: Mark.Bresnik@gilead.com


No publications provided


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
Study First Received: August 8, 2005
Results First Received: June 3, 2010
Last Updated: May 17, 2011
Health Authority: United States: Food and Drug Administration