International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (AIR-CF1)

March 21, 2011 updated by: Gilead Sciences

A Phase 3, Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary Pseudomonas Aeruginosa (AIR-CF1)

The purpose of this study was to evaluate the safety and efficacy of a 28-day course of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).

Study Overview

Detailed Description

CF patients often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called Pseudomonas aeruginosa (PA). Treatment with antibiotics can stop or slow down the growth of the bacteria. The antibiotics may be given by mouth, intravenously (IV), or by inhalation as a mist. The purpose of this study was to evaluate the safety and efficacy of AZLI, an investigational formulation of the antibiotic aztreonam and administered TID using the PARI eFlow® electronic nebulizer, in CF patients with PA.

In this study, participant eligibility was assessed at a screening visit 7 to 14 days prior to the baseline visit (Day 0). Those participants who continued to meet eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI TID or placebo TID). Participants returned for clinic visits at Day 14, an end of treatment visit at Day 28, and a follow-up visit 14 days after the last dose of study drug (Day 42).

Study Type

Interventional

Enrollment (Actual)

166

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Westmead, New South Wales, Australia
        • Westmead Hospital
      • Westmead, New South Wales, Australia
        • Children's Hospital at Westmead
    • Queensland
      • Herston, Queensland, Australia
        • Royal Children's Hospital
    • South Australia
      • Adelaide, South Australia, Australia
        • Royal Adelaide Hospital
    • Victoria
      • Prahran, Victoria, Australia
        • Alfred Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia
        • Sir Charles Gairdner Hospital
      • Perth, Western Australia, Australia
        • Princess Margaret Hospital for Children
    • Alberta
      • Edmonton, Alberta, Canada
        • Capital Health and the Governors of the University of Alberta
    • British Columbia
      • Vancouver, British Columbia, Canada
        • St. Paul's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Queen Elizabeth II Health Sciences Centre
    • Ontario
      • London, Ontario, Canada
        • Brian Lyttle Professional Corporation
    • Quebec
      • Montreal, Quebec, Canada
        • Centre Hospitalier de l'Université de Montreal (CHUM)
      • Auckland, New Zealand
        • Auckland District Health Board
    • Alabama
      • Birmingham, Alabama, United States
        • University of Alabama at Birmingham
    • Alaska
      • Anchorage, Alaska, United States
        • Pediatric Breathing Disorders Clinic
    • Arizona
      • Phoenix, Arizona, United States
        • Phoenix Children's Hospital
    • Arkansas
      • Little Rock, Arkansas, United States
        • University of Arkansas for Medical Sciences
    • California
      • Long Beach, California, United States
        • Miller Children's Hospital
      • Los Angeles, California, United States
        • Children's Hospital, Los Angeles
      • Orange, California, United States
        • Children's Hospital of Orange County
      • Sacramento, California, United States
        • Capital Allergy and Respiratory Disease Center
    • Connecticut
      • New Haven, Connecticut, United States
        • Yale New Haven Hospital
    • Florida
      • Gainesville, Florida, United States
        • University of Florida Health Sciences Center
      • Orlando, Florida, United States
        • Nemours Children's Clinic, Orlando
    • Georgia
      • Augusta, Georgia, United States
        • Medical College of Georgia
    • Illinois
      • Chicago, Illinois, United States
        • Children's Memorial Hospital / Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States
        • Riley Hospital for Children
    • Iowa
      • Iowa City, Iowa, United States
        • University of Iowa
    • Kansas
      • Wichita, Kansas, United States
        • Via Christi - St. Francis Regional Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States
        • Tulane University Health Sciences Center
      • Shreveport, Louisiana, United States
        • Louisiana State University Health Sciences Center
    • Maine
      • Auburn, Maine, United States
        • Central Maine Pulmonary Associates
    • Michigan
      • Ann Arbor, Michigan, United States
        • University of Michigan
    • Mississippi
      • Jackson, Mississippi, United States
        • University of Mississippi Medical Center
    • Missouri
      • Columbia, Missouri, United States
        • University of Missouri
      • St. Louis, Missouri, United States
        • St. Louis University
    • Nevada
      • Las Vegas, Nevada, United States
        • Children's Lung Specialists
    • New Jersey
      • Livingston, New Jersey, United States
        • St. Barnabas Healthcare System
    • New York
      • Albany, New York, United States
        • Albany Medical College
      • New Hyde Park, New York, United States
        • Long Island Jewish Medical Center
      • Syracuse, New York, United States
        • SUNY Upstate Medical University
    • North Carolina
      • Chapel Hill, North Carolina, United States
        • University of North Carolina
    • Ohio
      • Cincinnati, Ohio, United States
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • University of Pennsylvania Health System
      • Pittsburgh, Pennsylvania, United States
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Columbia, South Carolina, United States
        • Pediatric Pulmonary Associates, South Carolina
    • Texas
      • Dallas, Texas, United States
        • Baylor Martha Foster Lung Care Center
      • San Antonio, Texas, United States
        • Alamo Clinical Research Associates
    • Utah
      • Salt Lake City, Utah, United States
        • University of Utah
    • Virginia
      • Portsmouth, Virginia, United States
        • Naval Medical Center
      • Richmond, Virginia, United States
        • Pediatric Pulmonary Center/Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States
        • University of Washington Medical Center
    • Wisconsin
      • Madison, Wisconsin, United States
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

    • Sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);
    • Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
    • Abnormal nasal potential difference.
  • PA present in expectorated sputum or throat swab culture at Screening.
  • FEV1 between (and including) 25% and 75% predicted at Screening.
  • Negative pregnancy test at Screening.
  • Ability to perform reproducible pulmonary function tests.
  • Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
  • Ability to provide written informed consent.

Exclusion Criteria:

  • Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening.
  • 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.
  • Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer).
  • Known local or systemic hypersensitivity to monobactam antibiotics.
  • Inability to tolerate short-acting bronchodilator use at least three times daily.
  • Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit.
  • Changes in physiotherapy technique or schedule within 7 days prior to Screening or between Screening and the next visit.
  • History of lung transplantation.
  • A chest x-ray indicating abnormal findings at Screening or within the previous 90 days.
  • Abnormal renal or hepatic function at Screening.
  • 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.
  • Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo three times a day (TID)
Experimental: AZLI 75 mg three times a day (TID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CFQ-R Respiratory Symptoms Scale (RSS) Score
Time Frame: Day 0 to Day 28
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 respiratory symptoms scale (RSS; range of scores: 0-100; higher scores indicate fewer symptoms).
Day 0 to Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum
Time Frame: Day 0 to Day 28
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.
Day 0 to Day 28
Change in CFQ-R RSS Score
Time Frame: Day 0 to Day 14
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).
Day 0 to Day 14
Change in CFQ-R RSS Score
Time Frame: Day 0 to Day 42
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).
Day 0 to Day 42
Percent Change in FEV1 (L)
Time Frame: Day 0 to Day 28
Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. The percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was determined at Day 28.
Day 0 to Day 28
Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug
Time Frame: Day 0 to Day 42
Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.
Day 0 to Day 42
Number of Participants Hospitalized at Least Once Between Day 0 and Day 42
Time Frame: Day 0 to Day 42
Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.
Day 0 to Day 42

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Other Pathogens Present
Time Frame: Day 0 to Day 28
Sputum samples were collected at all visits for quantitative and qualitative culture for Staphylococcus aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans.
Day 0 to Day 28
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL)
Time Frame: Day 0

PA isolates from sputum samples (collected at all visits) were assessed for their susceptibility to aztreonam.

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.

Day 0
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL)
Time Frame: Day 28

PA isolates from sputum samples (collected at all visits) were assessed for their susceptibility to aztreonam.

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.

Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Bruce Montgomery, MD, Corus Pharma, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

April 1, 2007

Study Completion (Actual)

April 1, 2007

Study Registration Dates

First Submitted

June 1, 2005

First Submitted That Met QC Criteria

June 1, 2005

First Posted (Estimate)

June 2, 2005

Study Record Updates

Last Update Posted (Estimate)

April 21, 2011

Last Update Submitted That Met QC Criteria

March 21, 2011

Last Verified

March 1, 2011

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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