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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00128492




Registration number
NCT00128492
Ethics application status
Date submitted
8/08/2005
Date registered
10/08/2005
Date last updated
19/05/2011

Titles & IDs
Public title
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis (CF) Patients With Pseudomonas Aeruginosa (PA)
Scientific title
A Phase 3, Open-label, Follow-On Study of Multiple Courses of Aztreonam Lysinate for Inhalation (AI) in Cystic Fibrosis Patients (AIR-CF3)
Secondary ID [1] 0 0
CP-AI-006
Universal Trial Number (UTN)
Trial acronym
AIR-CF3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZLI 75 mg two times a day (BID)/ three times a day (TID)

Treatment: Drugs: AZLI 75 mg two times a day (BID)/ three times a day (TID)


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Reporting Adverse Events (AEs) - Participants experiencing at least 1 treatment-emergent AE or at least 1 serious adverse event (SAE) were summarized for the study as a whole. A treatment-emergent AE was any physical or clinical worsening in symptoms or disease experienced by the participant, whether or not the event was considered related to study participation or study procedures. An SAE was any adverse experience that resulted in hospitalization or death.
Participants were monitored for AEs and SAEs during all on-treatment and off-treatment intervals throughout the 18-month study period.
Timepoint [1] 0 0
Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Primary outcome [2] 0 0
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 - Airway reactivity (percent change in FEV1 from pretreatment to 30 minutes after treatment with AZLI) was assessed at all study visits in which a participant received AZLI treatment. A participant was included in this endpoint if they experienced a decline in FEV1 of =15% at any visit in which they received AZLI.
Timepoint [2] 0 0
Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Primary outcome [3] 0 0
Change in Heart Rate (HR) - HR was recorded at all visits.
Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Timepoint [3] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Primary outcome [4] 0 0
Change in Systolic and Diastolic Blood Pressure (BP) - BP was recorded at all visits.
Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Timepoint [4] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Primary outcome [5] 0 0
Change in Temperature - Temperature was recorded at all visits.
Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Timepoint [5] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Primary outcome [6] 0 0
Change in Respiratory Rate (RR) - RR was recorded at all visits.
Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Timepoint [6] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Primary outcome [7] 0 0
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets
Timepoint [7] 0 0
Baseline and end of Course 9 (Week 68)
Primary outcome [8] 0 0
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
Timepoint [8] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [9] 0 0
Serum Hematology - Number of Red Blood Cells (RBC)
Timepoint [9] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [10] 0 0
Serum Hematology - Hematocrit
Timepoint [10] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [11] 0 0
Serum Hematology - Hemoglobin
Timepoint [11] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [12] 0 0
Serum Hematology - Mean Corpuscular Volume (MCV)
Timepoint [12] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [13] 0 0
Serum Hematology - Mean Corpuscular Hemoglobin (MCH)
Timepoint [13] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [14] 0 0
Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)
Timepoint [14] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [15] 0 0
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)
Timepoint [15] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [16] 0 0
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen
Timepoint [16] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [17] 0 0
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium
Timepoint [17] 0 0
Baseline and end of treatment Course 9 (Week 68)
Primary outcome [18] 0 0
Serum Chemistry - Concentration of Total Protein
Timepoint [18] 0 0
Baseline and end of treatment Course 9 (Week 68)
Secondary outcome [1] 0 0
Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum - Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype).
Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.
Timepoint [1] 0 0
Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Secondary outcome [2] 0 0
Number of Participants With Other Pathogens - Sputum samples were collected at all study visits for qualitative and quantitative culture for Burkholderia cepacia complex (BCC), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Staphylococcus aureus (including methicillin-sensitive [MSSA] and methicillin-resistant [MRSA] S.aureus), and fungal organisms.
Number of participants with other pathogens at baseline and end of AZLI treatment Courses 1, 3, and 9 are reported.
Timepoint [2] 0 0
Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
Secondary outcome [3] 0 0
Minimum Inhibitory Concentration (MIC) of Aztreonam - The aztreonam susceptibility of PA isolates from expectorated sputum samples (collected at all visits) was assessed.
MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism).
MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism).
MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis.
Timepoint [3] 0 0
Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
Secondary outcome [4] 0 0
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) - Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines.
FEV1 = the volume of air exhaled in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudson equation, based upon participant age, gender, and height. FVC = (forced vital capacity) the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC.
The percent change from baseline is presented for each endpoint.
Timepoint [4] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Secondary outcome [5] 0 0
Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) - The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms). The minimal clinically important difference (MCID) corresponds to the smallest change in symptoms that a patient can detect and is a change in score of 4 points.
Timepoint [5] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Secondary outcome [6] 0 0
Time to First Hospitalization Due to a Respiratory Event - Details of all hospitalizations, including the dates of admission and discharge, were recorded on the serious adverse event (SAE) electronic case report form (eCRF).
Time to first hospitalization was the number of days from baseline (Visit 1) to the date of first hospitalization or the date of study completion (last visit) /or early withdrawal if censored.
Timepoint [6] 0 0
Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Secondary outcome [7] 0 0
Change in Body Weight - Weight was measured at all visits and was reported to the nearest 0.1 kg/lb. Percent change in weight from baseline was calculated.
Timepoint [7] 0 0
Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Secondary outcome [8] 0 0
Missed School/Work Days Due to CF Symptoms - Participants were provided with a diary card at each visit to record days of work and/or school missed due to their CF symptoms.
The percentage of school/work days missed was calculated as the total number of school/work days missed divided by the total number of on-study days multiplied by 100 across all participants in a treatment group.
Timepoint [8] 0 0
Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Secondary outcome [9] 0 0
Time to Intravenous (IV) Antipseudomonal Antibiotics - Use of IV antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF. The time to first IV antipseudomonal antibiotic use was the number of days from baseline (Visit 1) to the date of first IV antipseudomonal antibiotic use or the date of study completion (last visit) /or early withdrawal if censored.
Timepoint [9] 0 0
Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Eligibility
Key inclusion criteria
- Compliance with Studies CP-AI-005 (NCT00104520) or CP-AI-007 (NCT00112359) by taking
at least 50% of expected study medication.

- Completion of CP-AI-005 or CP-AI-007 or was withdrawn due to need for antipseudomonal
antibiotics or for an AE unrelated to study medication tolerance.

- Ability to provide written informed consent/assent prior to initiation of
study-related procedures.

- Ability to perform reproducible pulmonary function tests.
Minimum age
6 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Use of any investigational medication or device between the last visit of CP-AI-005 or
CP-AI-007 and Visit 1 of this study.

- Concurrent participation in a study of another investigational drug or device.

- Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg
prednisone/day or 20 mg prednisone every other day.

- History of sputum or throat swab culture yielding Burkholderia cepacia in the previous
2 years.

- History of daily continuous oxygen supplementation or requirement for more than 2
liters/minute at night.

- Inability to tolerate study medication in CP-AI-005 or CP-AI-007.

- Known local or systemic hypersensitivity to aztreonam.

- Inability to tolerate inhalation of a short acting beta-2 agonist.

- Abnormal renal or hepatic function based on results of most recent test.

- Female of child-bearing potential who was pregnant, lactating, or not (in the opinion
of the investigator) practicing an acceptable method of birth control.

- Any serious or active medical or psychiatric illness which, in the opinion of the
investigator, would have interfered with participant treatment, assessment, or
compliance with the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
- Westmead
Recruitment hospital [2] 0 0
- Herston
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Prahan
Recruitment hospital [5] 0 0
- Nedlands
Recruitment hospital [6] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- Prahan
Recruitment postcode(s) [5] 0 0
- Nedlands
Recruitment postcode(s) [6] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Massachusetts
Country [15] 0 0
United States of America
State/province [15] 0 0
Michigan
Country [16] 0 0
United States of America
State/province [16] 0 0
Minnesota
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
Nevada
Country [19] 0 0
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State/province [19] 0 0
New Jersey
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
State/province [23] 0 0
Oklahoma
Country [24] 0 0
United States of America
State/province [24] 0 0
Pennsylvania
Country [25] 0 0
United States of America
State/province [25] 0 0
South Carolina
Country [26] 0 0
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State/province [26] 0 0
Texas
Country [27] 0 0
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State/province [27] 0 0
Utah
Country [28] 0 0
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State/province [28] 0 0
Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
Washington
Country [30] 0 0
United States of America
State/province [30] 0 0
West Virginia
Country [31] 0 0
Canada
State/province [31] 0 0
Alberta
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
New Zealand
State/province [33] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to evaluate the safety and efficacy of multiple courses of AZLI
in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).
Trial website
https://clinicaltrials.gov/show/NCT00128492
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bruce Montgomery, MD
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications