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

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

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)

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 ]

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.