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

History of Changes

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

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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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

Description

75 mg AZLI Two Times a Day (BID)

BID = twice daily

75 mg AZLI Three Times a Day (TID)

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

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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 ]

Show Outcome Measure 1

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 ]

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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) ]

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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) ]

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5. Primary:

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

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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) ]

Show Outcome Measure 6

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) ]

Show Outcome Measure 7

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) ]

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9. Primary:

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

Show Outcome Measure 9

10. Primary:

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

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11. Primary:

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

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12. Primary:

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

Show Outcome Measure 12

13. Primary:

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

Show Outcome Measure 13

14. Primary:

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

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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) ]

Show Outcome Measure 15

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) ]

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17. Primary:

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

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18. Primary:

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

Show Outcome Measure 18

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) ]

Show Outcome Measure 19

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) ]

Show Outcome Measure 20

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) ]

Show Outcome Measure 21

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) ]

Show Outcome Measure 22

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) ]

Show Outcome Measure 23

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 ]

Show Outcome Measure 24

25. Secondary:

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

Show Outcome Measure 25

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 ]

Show Outcome Measure 26

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 ]

Show Outcome Measure 27

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Institution and investigator may publish or present the results of the trial generated there with prior written consent of Gilead; or 2 years after the trial has ended at all institutions. Proposed publications/target venue must go to Gilead 30 days (manuscripts) or 15 days (abstracts/presentations) prior. Any Gilead confidential information in the document(s) must be deleted or, if requested publication, delayed for up to 45 days to permit Gilead to obtain intellectual property protection.

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

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