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

Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Cystic Fibrosis; Lung Infection; Pseudomonas Aeruginosa

Intervention: AZLI 75 mg three times daily (TID) (Drug); Placebo three times daily (TID) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Gilead Sciences

Official(s) and/or principal investigator(s):
Claire Wainwright, MD, Principal Investigator, Affiliation: Royal Children's Hospital, Brisbane, QLD, Australia
Ron Gibson, MD, Principal Investigator, Affiliation: Children's Hospital & Regional Medical Center, Seattle WA, USA

Summary

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), mild lung disease (forced expiratory volume in 1 second [FEV1] >75% predicted, and Pseudomonas aeruginosa (PA) infection.

Clinical Details

Official title: A Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysine For Inhalation in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (AIR-CF4)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28

Secondary outcome:

Change From Baseline in CFQ-R RSS Score at Day 14

Change From Baseline in CFQ-R RSS Score at Day 42

Change From Baseline in CFQ-R Physical Functioning Domain Score

Number of Participants Using Additional (Nonprotocol-specified) Antipseudomonal Antibiotics During Study

Number of Participants Hospitalized During Study

Change From Baseline in Log10 Pseudomonas Aeruginosa (PA) Colony Forming Units (CFUs) in Sputum at Day 28

Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted

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 three times a day using the PARI eFlow® electronic nebulizer, in CF patients with PA and mild lung disease. In this study, participant eligibility was assessed at a screening visit that occurred up to 14 days prior to the baseline visit (Day 0). Those participants who met eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI 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 the trial drug (Day 42).

Eligibility

Minimum age: 6 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Participants ≥ 6 years of age

- 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 ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test

- Two well characterized mutations in the cystic fibrosis transmembrane

conductance regulator (CFTR) gene

- Abnormal nasal potential difference

- PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA

in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1 (one of the previous PA positive cultures must have been no more than 3 months prior to Visit 1)

- FEV1 > 75% predicted at Visit 1

- Participants must have exhibited two or more of the following chronic and/or

intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no worsening of symptoms within 7 days prior to randomization:

- Chest congestion

- Daily cough

- Productive cough

- Wheezing

- Trouble breathing

- Nocturnal wakening due to coughing

- Participants (and parent/guardian as required) had to be able to provide written

informed consent/assent prior to any study related procedures

- Females of childbearing potential had to have a negative urine pregnancy test at

Visit 1

- Ability to perform reproducible pulmonary function tests

- In the opinion of the Investigator, the participant did not require immediate

antipseudomonal antibiotic intervention to treat an impending exacerbation, and the participant's condition was stable enough to enroll in the study Exclusion Criteria:

- Administration of any investigational drug or device within 28 days prior to Visit 1

or within 6 half-lives of the investigational drug (whichever was longer)

- Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days

prior to Visit 1

- Known local or systemic hypersensitivity to monobactam antibiotics

- Inability to tolerate short-acting bronchodilator (BD) use at least TID

- Changes in or initiation of chronic azithromycin treatment within 28 days prior to

Visit 1

- Changes in or initiation of chronic hypertonic saline treatment within 28 days prior

to Visit 1

- Changes in or initiation of dornase alfa within 28 days prior to Visit 1

- Changes in antimicrobial, BD, or corticosteroid medications within 7 days prior to

Visit 1

- Changes in physiotherapy technique or schedule within 7 days prior to Visit 1

- History of lung transplantation

- History of participation (enrollment) in any prior clinical studies with AZLI

- A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with

abnormalities indicating a significant acute finding (e. g., lobar infiltrate and atelectasis, pneumothorax, or pleural effusion); a chest radiograph obtained and interpreted between Visits 1 and 2 was also acceptable for determining eligibility

- Positive urine pregnancy test at Visit 1; all women of childbearing potential were to

be tested

- Females of childbearing potential who were lactating or were not (in the opinion of

the investigator) practicing an acceptable method of birth control; female participants who utilized hormonal contraceptives as their birth control method must have used the same method for at least 3 months before study dosing

- Participant was being assessed at Visit 1 by the investigator for an acute change in

respiratory symptoms

- 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

Locations and Contacts

Phoenix Children's Hospital, Phoenix, Arizona, United States

University Medical Center, Tucson, Arizona, United States

Arkansas Children's Hospital, Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences, Division of Pulmonary and Critical Care Medicine, Little Rock, Arkansas, United States

Kaiser Permanente, Oakland, California, United States

Children's Hospital of Orange County, Orange, California, United States

The Children's Hospital, Aurora, Colorado, United States

Connecticut Children's Medical Center, Hartford, Connecticut, United States

Nemours Children's Clinic, Jacksonville, Florida, United States

Nemours Children's Clinic, Orlando, Florida, United States

Children's Memorial Hospital, Chicago, Illinois, United States

Indiana University, Outpatient Clinical Research Facility, Indianapolis, Indiana, United States

James Whitcomb Riley Hospital for Children, Indianapolis, Indiana, United States

Children's Hospital, Boston, Boston, Massachusetts, United States

Tufts Medical Center, Pediatric Pulmonary Clinic, Boston, Massachusetts, United States

University of Michigan Health System, Ann Arbor, Michigan, United States

The Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan, United States

The Minnesota CF Center, University of Minnesota Medical Center, Minneapolis, Minnesota, United States

Children's Lung Specialists, Las Vegas, Nevada, United States

Department of Respiratory Medicine, The Children's Hospital at Westmead, Westmead, New South Wales, Australia

Department of Respiratory Medicine, Westmead Hospital, Westmead, New South Wales, Australia

Albany Medical College, Albany, New York, United States

The Lung & Cystic Fibrosis Center, University of Buffalo Pediatric Associates, Inc., Women & Children's Hospital of Buffalo, Buffalo, New York, United States

Long Island Jewish Medical Center, New Hyde Park, New York, United States

SUNY Upstate Medical University, Syracuse, New York, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Nationwide Children's Hospital, Columbus, Ohio, United States

Toledo Children's Hospital/Toledo Hospital, Cystic Fibrosis Research Center, Toledo, Ohio, United States

Santiago Reyes, MD, Oklahoma City, Oklahoma, United States

Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States

Drexel University College of Medicine, Pulmonary Associates, Philadelphia, Pennsylvania, United States

Penn Presbyterian Medical Center, Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States

Centre de Recherche du CHUM, Montreal, Quebec, Canada

The Prince Charles Hospital, Adult Cystic Fibrosis Centre, Chermside, Queensland, Australia

Respiratory Medicine, Royal Children's Hospital, Herston, Queensland, Australia

Baylor College of Medicine, Houston, Texas, United States

Primary Children's Medical Center, Salt Lake City, Utah, United States

Children's Hospital and Regional Medical Center, Seattle, Washington, United States

Child and Adolescent Health Services, Princess Margaret Hospital, Perth, Western Australia, Australia

Additional Information

Starting date: May 2008
Last updated: November 19, 2010

Page last updated: August 20, 2015

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