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

NCT ID: NCT00712166

Last Updated: 2010-12-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2009-08-31

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Cystic Fibrosis Lung Infection Pseudomonas Aeruginosa

Keywords

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cystic fibrosis pseudomonas aeruginosa lung infection CFQ-R inhaled antibiotic aztreonam lysine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo three times daily (TID)

Group Type PLACEBO_COMPARATOR

Placebo three times daily (TID)

Intervention Type DRUG

AZLI 75 mg three times daily (TID)

Group Type EXPERIMENTAL

AZLI 75 mg three times daily (TID)

Intervention Type DRUG

Interventions

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AZLI 75 mg three times daily (TID)

Intervention Type DRUG

Placebo three times daily (TID)

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Gilead Sciences, Inc.

Principal Investigators

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Claire Wainwright, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Children's Hospital, Brisbane, QLD, Australia

Ron Gibson, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital & Regional Medical Center, Seattle WA, USA

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

University Medical Center

Tucson, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences, Division of Pulmonary and Critical Care Medicine

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

The Children's Hospital

Aurora, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

Nemours Children's Clinic

Orlando, Florida, United States

Site Status

Children's Memorial Hospital

Chicago, Illinois, United States

Site Status

Indiana University, Outpatient Clinical Research Facility

Indianapolis, Indiana, United States

Site Status

James Whitcomb Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Children's Hospital, Boston

Boston, Massachusetts, United States

Site Status

Tufts Medical Center, Pediatric Pulmonary Clinic

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

The Children's Hospital of Michigan, Detroit Medical Center

Detroit, Michigan, United States

Site Status

The Minnesota CF Center, University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status

Children's Lung Specialists

Las Vegas, Nevada, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

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

Buffalo, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Toledo Children's Hospital/Toledo Hospital, Cystic Fibrosis Research Center

Toledo, Ohio, United States

Site Status

Santiago Reyes, MD

Oklahoma City, Oklahoma, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Drexel University College of Medicine, Pulmonary Associates

Philadelphia, Pennsylvania, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center

Seattle, Washington, United States

Site Status

Department of Respiratory Medicine, The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Site Status

Department of Respiratory Medicine, Westmead Hospital

Westmead, New South Wales, Australia

Site Status

The Prince Charles Hospital, Adult Cystic Fibrosis Centre

Chermside, Queensland, Australia

Site Status

Respiratory Medicine, Royal Children's Hospital

Herston, Queensland, Australia

Site Status

Child and Adolescent Health Services, Princess Margaret Hospital

Perth, Western Australia, Australia

Site Status

Centre de Recherche du CHUM

Montreal, Quebec, Canada

Site Status

Countries

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United States Australia Canada

References

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Wainwright CE, Quittner AL, Geller DE, Nakamura C, Wooldridge JL, Gibson RL, Lewis S, Montgomery AB. Aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis, mild lung impairment, and P. aeruginosa. J Cyst Fibros. 2011 Jul;10(4):234-42. doi: 10.1016/j.jcf.2011.02.007. Epub 2011 Mar 26.

Reference Type DERIVED
PMID: 21441078 (View on PubMed)

Other Identifiers

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GS-US-205-0117

Identifier Type: -

Identifier Source: org_study_id