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Cystic FibrosisPhase 3AIR-CF3NCT00128492

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

A Phase 3 study testing AZLI 75 mg two times a day (BID)/ three times a day (TID) in people with Cystic Fibrosis, run by Gilead Sciences at 65 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 6 years and older
Conditions the study is for
Cystic Fibrosis
What is being tested?
AZLI 75 mg two times a day (BID)/ three times a day (TID)
How many people
274 participants
Where
65 sitesin 4 countries
Study dates
Aug 2005to Jan 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

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  • Completion of CP-AI-005 or CP-AI-007 or was withdrawn due to need for antipseudomonal antibiotics or for an AE unrelated to study medication tolerance.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

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

65 sites in 4 countries.

65 sites in 4 countries

United States56 sites

  • Study site

    Akron, Ohio

  • Study site

    Albany, New York

  • Study site

    Anchorage, Alaska

  • Study site

    Ann Arbor, Michigan

  • Study site

    Atlanta, Georgia

  • Study site

    Augusta, Georgia

  • Study site

    Birmingham, Alabama

  • Study site

    Boston, Massachusetts

  • Study site

    Brooklyn, New York

  • Study site

    Buffalo, New York

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Columbia, Missouri

  • Study site

    Columbia, South Carolina

  • Study site

    Columbus, Ohio

  • Study site

    Dayton, Ohio

  • Study site

    Denver, Colorado

  • Study site

    Detroit, Michigan

  • Study site

    Glenview, Illinois

  • Study site

    Hartford, Connecticut

  • Study site

    Hershey, Pennsylvania

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Jacksonville, Florida

  • Study site

    La Jolla, California

  • Study site

    Las Vegas, Nevada

  • Study site

    Little Rock, Arkansas

  • Study site

    Livingston, New Jersey

  • Study site

    Los Angeles, California

  • Study site

    Maywood, Illinois

  • Study site

    Minneapolis, Minnesota

  • Study site

    Morgantown, West Virginia

  • Study site

    Morristown, New Jersey

  • Study site

    New Haven, Connecticut

  • Study site

    New Hyde Park, New York

  • Study site

    New York, New York

  • Study site

    Oakland, California

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Orange, California

  • Study site

    Orlando, Florida

  • Study site

    Park Ridge, Illinois

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Phoenix, Arizona

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Portsmouth, Virginia

  • Study site

    Richmond, Virginia

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    Seattle, Washington

  • Study site

    Shreveport, Louisiana

  • Study site

    St Louis, Missouri

  • Study site

    Syracuse, New York

  • Study site

    Valhalla, New York

  • Study site

    Wichita, Kansas

Other trials in United States

Australia6 sites

  • Study site

    Adelaide, South Australia

  • Study site

    Herston, Queensland

  • Study site

    Nedlands, Western Australia

  • Study site

    Perth, Western Australia

  • Study site

    Prahan, Victoria

  • Study site

    Westmead, New South Wales

Other trials in Australia

Canada2 sites

  • Study site

    Edmonton, Alberta

  • Study site

    London, Ontario

Other trials in Canada

New Zealand1 site

  • Study site

    Auckland

Other trials in New Zealand

About this study

Official title: A Phase 3, Open-label, Follow-On Study of Multiple Courses of Aztreonam Lysinate for Inhalation (AI) in Cystic Fibrosis Patients (AIR-CF3)

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).

Read the detailed description

People with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by PA. Treatment with antibiotics is used to reduce the presence of the bacteria. The antibiotics may be given orally, intravenously, or inhaled as a mist. The purpose of this study was to evaluate whether AZLI, an investigational formulation of the antibiotic aztreonam, is safe in repeated courses in patients with CF and PA.

A course of AZLI treatment in this study comprised 28 days, followed by a 28-day period off treatment. Participants could receive up to 9 courses of AZLI, with a total time on study of up to 18 months. Safety and efficacy results for the 18-month, 9-course period are reported, with efficacy results presented on a by-treatment course basis.

Conditions
Cystic Fibrosis
Being tested
AZLI 75 mg two times a day (BID)/ three times a day (TID)
Keywords
cystic fibrosis, Pseudomonas aeruginosa
Medical subject headings
Cystic Fibrosis, Pseudomonas Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZLI 75 mg two times a day (BID)/ three times a day (TID)Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

  2. 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.

    Measured: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

  3. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

  4. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

  5. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

  6. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

  7. Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets

    Measured: Baseline and end of Course 9 (Week 68)

  8. Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils

    Measured: Baseline and end of treatment Course 9 (Week 68)

  9. Serum Hematology - Number of Red Blood Cells (RBC)

    Measured: Baseline and end of treatment Course 9 (Week 68)

  10. Serum Hematology - Hematocrit

    Measured: Baseline and end of treatment Course 9 (Week 68)

  11. Serum Hematology - Hemoglobin

    Measured: Baseline and end of treatment Course 9 (Week 68)

  12. Serum Hematology - Mean Corpuscular Volume (MCV)

    Measured: Baseline and end of treatment Course 9 (Week 68)

  13. Serum Hematology - Mean Corpuscular Hemoglobin (MCH)

    Measured: Baseline and end of treatment Course 9 (Week 68)

  14. Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)

    Measured: Baseline and end of treatment Course 9 (Week 68)

  15. Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)

    Measured: Baseline and end of treatment Course 9 (Week 68)

  16. Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen

    Measured: Baseline and end of treatment Course 9 (Week 68)

  17. Serum Chemistry - Concentration of Chloride, Potassium, and Sodium

    Measured: Baseline and end of treatment Course 9 (Week 68)

  18. Serum Chemistry - Concentration of Total Protein

    Measured: Baseline and end of treatment Course 9 (Week 68)

Secondary outcomes (9)

  1. 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.

    Measured: Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

  2. 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.

    Measured: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)

  3. 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.

    Measured: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)

  4. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

  5. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

  6. 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.

    Measured: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

  7. 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.

    Measured: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

  8. 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.

    Measured: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

  9. 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.

    Measured: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2005 (estimated)
  2. Study startAug 2005
  3. Primary completionNov 2008
  4. Study completionJan 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Masking
None (open label)
Enrolment
274 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00128492
Sponsor's protocol ID
CP-AI-006
Acronym
AIR-CF3
Status last verified
May 2011
First submitted
8 Aug 2005
Last updated
19 May 2011
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AZLI 75 mg two times a day (BID)/ three times a day (TID) in people with Cystic Fibrosis, run by Gilead Sciences at 65 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, Australia, Canada, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00128492.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2011.

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