Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (AIR-CF2)

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00104520
First received: March 1, 2005
Last updated: February 16, 2011
Last verified: September 2010
  Purpose

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


Condition Intervention Phase
Cystic Fibrosis
Drug: AZLI 75 mg two times a day (BID)/three times a day (TID)
Drug: Placebo two times a day (BID)/three times a day (TID)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial With Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary P. Aeruginosa Requiring Frequent Antibiotics (AIR-CF2)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics [ Time Frame: Day 0 to Day 84 (end of study) ] [ Designated as safety issue: No ]
    The primary endpoint was time to need for a course of inhaled or IV antipseudomonal antibiotics with documented physician assessment of need for antibiotics. Antipseudomonal Antibiotic need was documented based on the presence of at least one of the following four symptoms predictive of pulmonary exacerbation: decreased exercise tolerance, increased cough, increased sputum / chest congestion, decreased appetite, or other.


Secondary Outcome Measures:
  • Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]
    The CFQ-R was administered at Day -28, baseline, Day 14, Day 28, and Day 84 (end of study). The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores [units]: 0-100; higher scores indicate fewer symptoms).

  • Percent Change in Forced Expiratory Volume in 1 Second (FEV1) (L) [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]

    Spirometry was performed at each visit. FEV1 was recorded according to American Thoracic Society (ATS) guidelines.

    FEV1(L) is the measurement of the volume of air (expressed in liters) exhaled in 1 second.

    The percent change in this parameter from Day 0 to Day 28 was determined for each treatment group.


  • Number of Hospitalization Days [ Time Frame: Day 0 to Day 84 ] [ Designated as safety issue: No ]
    Details of all hospitalizations, including the dates of admission and discharge, were recorded on the electronic case report form (eCRF).

  • Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 211
Study Start Date: February 2005
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo (pooled two times a day [BID]/three times a day [TID]) Drug: Placebo two times a day (BID)/three times a day (TID)
Experimental: AZLI (pooled two times a day [BID]/three times a day [TID]) Drug: AZLI 75 mg two times a day (BID)/three times a day (TID)

Detailed Description:

Patients with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called 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 aztreonam for inhalation solution (AZLI), an investigational formulation of the antibiotic administered using the eFlow® Electronic Nebulizer by PARI GmbH, in CF patients with PA.

In this study, participants were screened for eligibility at Visit 1 (Day -42) and returned to the center for Visit 2 after a 14-day evaluation period. At Visit 2 (Day -28), participants began a 28-day course of open-label Tobramycin Inhalation Solution (TIS). At Visit 3 (Day 0), following completion of the 28-day course of TIS, participants began randomized, blinded treatment with either AZLI twice a day (BID) or three times a day (TID) or placebo BID or TID, and continued treatment for a total of 28 days, with a clinic visit at Day 14 (Visit 4) and at the end of treatment (Visit 5 [Day 28]). Participants returned for visits every 2 weeks for 8 weeks after the end of the blinded treatment (Visits 6 to 9 [Days 42 to 84]).

Two hundred and forty-seven participants were treated in the TIS phase of this study. Two hundred and eleven subjects completed the TIS phase and were treated in the placebo-controlled phase with study drug (AZLI or placebo).

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CF as diagnosed by:

    1. Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test; or
    2. Two well-characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
    3. Abnormal nasal potential difference with accompanying symptoms characteristic of CF.
  • PA present in expectorated sputum or throat swab culture at Screening.
  • Participants must have received three or more courses of TIS within the previous 12 months.
  • Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
  • Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
  • Ability to perform reproducible pulmonary function tests.
  • Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.

Exclusion Criteria:

  • Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day.
  • History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2 years.
  • History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
  • Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
  • Known local or systemic hypersensitivity to monobactam antibiotics.
  • Inability to tolerate inhalation of a short acting Beta-2 agonist.
  • Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days before Screening or between Screening and the next visit.
  • Changes in physiotherapy technique or schedule within 7 days before 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 or serum chemistry at Screening (aspartate aminotransferase [AST], alanine aminotransferase [ALT] greater than 5 times the upper limit of normal range; Creatinine greater than 2 times the upper limit of normal range).
  • Positive pregnancy test at Screening.
  • Female of childbearing potential who was lactating or in the opinion of the investigator was not practicing acceptable 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00104520

  Hide Study Locations
Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
United States, California
University of California, San Diego
La Jolla, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Kaiser Permanente Medical Care Program
Oakland, California, United States
Children's Hospital, Orange Co.
Orange, California, United States
Stanford University Hospital and Medical Center
Palo Alto, California, United States
UC Davis Medical Center
Sacramento, California, United States
United States, Colorado
Children's Hospital
Denver, Colorado, United States
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States
United States, Florida
University of Florida Health Sciences Center
Gainesville, Florida, United States
Nemours Children's Clinic, Jacksonville
Jacksonville, Florida, United States
University of Miami School of Medicine
Miami, Florida, United States
Nemours Children's Clinic
Orlando, Florida, United States
Pediatric Pulmonary Associates, Florida
St. Petersburg, Florida, United States
United States, Georgia
Emory Healthcare
Atlanta, Georgia, United States
Medical College of Georgia
Augusta, Georgia, United States
United States, Illinois
Children's Memorial Hospital/Northwestern University
Chicago, Illinois, United States
Chicago Children's Asthma Respiratory and Exercise Specialists
Glenview, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
North Suburban Pulmonary / Critical Care Consultants
Niles, Illinois, United States
United States, Indiana
Indiana University
Indianapolis, Indiana, United States
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States
United States, Maine
Maine Medical Center
Portland, Maine, United States
United States, Massachusetts
Floating Hospital for Children
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Children's Hospital, Boston
Boston, Massachusetts, United States
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States
Children's Hospital of Michigan/Wayne State University
Detroit, Michigan, United States
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
United States, Nevada
Children's Lung Specialists, Ltd.
Las Vegas, Nevada, United States
United States, New Jersey
Morristown Memorial Hospital
Morristown, New Jersey, United States
United States, New York
Albany Medical College
Albany, New York, United States
Long Island College Hospital
Brooklyn, New York, United States
Children's Hospital of Buffalo
Buffalo, New York, United States
Long Island Jewish Medical Center
New Hyde Park, New York, United States
Columbia University Medical Center
New York, New York, United States
State University of New York Stony Brook
Stony Brook, New York, United States
Children's Hospital of Westchester Medical Center/New York Medical College
Valhalla, New York, United States
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States
Columbus Children's Hospital, Ohio State University
Columbus, Ohio, United States
Children's Medical Center
Dayton, Ohio, United States
United States, Oklahoma
Dr. Santiago Reyes
Oklahoma City, Oklahoma, United States
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States
United States, Pennsylvania
Penn State University Hershey Medical Center
Hershey, Pennsylvania, United States
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburg
Pittsburg, Pennsylvania, United States
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States
Pediatric Pulmonary Associates, South Carolina
Columbia, South Carolina, United States
United States, Texas
Baylor College of Medicine
Houston, Texas, United States
Alamo Clinical Research Associates
San Antonio, Texas, United States
United States, Virginia
Pediatric Pulmonary Center
Richmond, Virginia, United States
United States, Washington
Children's Hospital and Regional Medical Center
Seattle, Washington, United States
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States
Sponsors and Collaborators
Gilead Sciences
Investigators
Principal Investigator: Karen McCoy, MD Nationwide Children's Hospital
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mark Bresnik, MD, Director, Clinical Research, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier: NCT00104520     History of Changes
Other Study ID Numbers: CP-AI-005
Study First Received: March 1, 2005
Results First Received: September 10, 2010
Last Updated: February 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Cystic Fibrosis
Pseudomonas aeruginosa
Pulmonary Cystic Fibrosis

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014