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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)

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 
Overall Participants Analyzed 
[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 
[1] 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] 
[Units: Participants]
     
FEV1 > 50% predicted   49   114   163 
FEV1 ≤ 50% predicted   36   74   110 
Unknown   0   1   1 
[1] 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) 
[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) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 65.410  (16.896)   60.332  (18.497)   61.895  (18.141) 
[1] CFQ-R RSS scale range 0-100, with higher scores indicating fewer CF symptoms.
Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted [1] 
[Units: Percent]
Mean (Standard Deviation)
 56.711  (17.505)   55.071  (15.428)   55.582  (16.089) 
[1] 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 
[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) 


  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


  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
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.


  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: Mark Bresnik, Director of Clinical Research
Organization: Gilead Sciences, Inc.
phone: 650-522-5934
e-mail: Mark.Bresnik@gilead.com



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