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

NCT ID: NCT00104520

Last Updated: 2011-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2006-09-30

Brief Summary

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).

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).

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo (pooled two times a day [BID]/three times a day [TID])

Group Type: PLACEBO_COMPARATOR

Placebo two times a day (BID)/three times a day (TID)

Intervention Type: DRUG

AZLI (pooled two times a day [BID]/three times a day [TID])

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Interventions

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

Intervention Type: DRUG

Placebo two times a day (BID)/three times a day (TID)

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Gilead Sciences, Inc.

Principal Investigators

Karen McCoy, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

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

Children's Hospital

Denver, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

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

Emory Healthcare

Atlanta, Georgia, United States

Medical College of Georgia

Augusta, Georgia, United States

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

Indiana University

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Maine Medical Center

Portland, Maine, United States

Children's Hospital, Boston

Boston, Massachusetts, United States

Floating Hospital for Children

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Children's Hospital of Michigan/Wayne State University

Detroit, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Lung Specialists, Ltd.

Las Vegas, Nevada, United States

Morristown Memorial Hospital

Morristown, New Jersey, United States

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

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

Dr. Santiago Reyes

Oklahoma City, Oklahoma, United States

Oregon Health & Science University

Portland, Oregon, United States

Penn State University Hershey Medical Center

Hershey, Pennsylvania, United States

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburg

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Pediatric Pulmonary Associates, South Carolina

Columbia, South Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

Alamo Clinical Research Associates

San Antonio, Texas, United States

Pediatric Pulmonary Center

Richmond, Virginia, United States

Children's Hospital and Regional Medical Center

Seattle, Washington, United States

West Virginia University

Morgantown, West Virginia, United States

Countries

United States

References

Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009 Jun;135(6):1610-1618. doi: 10.1378/chest.08-1190. Epub 2009 May 15.

Reference Type: DERIVED

PMID: 19447923 (View on PubMed)

McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008 Nov 1;178(9):921-8. doi: 10.1164/rccm.200712-1804OC. Epub 2008 Jul 24.

Reference Type: DERIVED

PMID: 18658109 (View on PubMed)

Other Identifiers

CP-AI-005

Identifier Type: -

Identifier Source: org_study_id