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

NCT00712166 | Completed Phase 3 Results DMC

• 1 other identifier: GS-US-205-0117
• Study Type: interventional
• Target: 160
• Locations: 3 countries
• Sites: 40

Brief 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.

Conditions

Cystic Fibrosis; Lung Infection; Pseudomonas Aeruginosa

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.

  Day 0 to Day 28

Secondary Outcomes (7)

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

  Day 0 to Day 14

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

  Day 0 to Day 42

• Change From Baseline in CFQ-R Physical Functioning Domain Score

  Day 0 to Day 28

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

  Day 0 to Day 42

• Number of Participants Hospitalized During Study

  Day 0 to Day 42

Other Outcomes (2)

• Number of Participants Testing Positive for Other Respiratory Pathogens

  Day 0 to Day 28

• The Minimum Concentrations of Aztreonam That Inhibit 50% and 90% of All PA Isolates (MIC50 and MIC90, Respectively)

  Day 0 to Day 28

Study Arms (2)

Placebo three times daily (TID)

PLACEBO COMPARATOR

Drug: Placebo three times daily (TID)

AZLI 75 mg three times daily (TID)

EXPERIMENTAL

Drug: AZLI 75 mg three times daily (TID)

Interventions

AZLI 75 mg three times daily (TID) DRUG

AZLI 75 mg three times daily (TID)

Placebo three times daily (TID) DRUG

Placebo three times daily (TID)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (40)

Phoenix Children's Hospital

Phoenix, Arizona, United States

Location

University Medical Center

Tucson, Arizona, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Location

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

Little Rock, Arkansas, United States

Location

Kaiser Permanente

Oakland, California, United States

Location

Children's Hospital of Orange County

Orange, California, United States

Location

The Children's Hospital

Aurora, Colorado, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, United States

Location

Nemours Children's Clinic

Orlando, Florida, United States

Location

Children's Memorial Hospital

Chicago, Illinois, United States

Location

Indiana University, Outpatient Clinical Research Facility

Indianapolis, Indiana, United States

Location

James Whitcomb Riley Hospital for Children

Indianapolis, Indiana, United States

Location

Children's Hospital, Boston

Boston, Massachusetts, United States

Location

Tufts Medical Center, Pediatric Pulmonary Clinic

Boston, Massachusetts, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, United States

Location

The Children's Hospital of Michigan, Detroit Medical Center

Detroit, Michigan, United States

Location

The Minnesota CF Center, University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Location

Children's Lung Specialists

Las Vegas, Nevada, United States

Location

Albany Medical College

Albany, New York, United States

Location

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

Buffalo, New York, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Location

SUNY Upstate Medical University

Syracuse, New York, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, United States

Location

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

Toledo, Ohio, United States

Location

Santiago Reyes, MD

Oklahoma City, Oklahoma, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Location

Drexel University College of Medicine, Pulmonary Associates

Philadelphia, Pennsylvania, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Location

Baylor College of Medicine

Houston, Texas, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, United States

Location

Children's Hospital and Regional Medical Center

Seattle, Washington, United States

Location

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

Westmead, New South Wales, Australia

Location

Department of Respiratory Medicine, Westmead Hospital

Westmead, New South Wales, Australia

Location

The Prince Charles Hospital, Adult Cystic Fibrosis Centre

Chermside, Queensland, Australia

Location

Respiratory Medicine, Royal Children's Hospital

Herston, Queensland, Australia

Location

Child and Adolescent Health Services, Princess Margaret Hospital

Perth, Western Australia, Australia

Location

Centre de Recherche du CHUM

Montreal, Quebec, Canada

Location

Related Publications (1)

• 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.

  PMID: 21441078 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Mark Bresnik, MD, Director, Clinical Research
• Organization: Gilead Sciences, Inc.

mark.bresnik@gilead.com

(650) 522-5934

Study Officials

• Claire Wainwright, MD

  Royal Children's Hospital, Brisbane, QLD, Australia

  PRINCIPAL INVESTIGATOR

• Ron Gibson, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 7, 2008
• First Posted: July 9, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: August 1, 2009
• Last Updated: December 20, 2010
• Results First Posted: December 20, 2010

Record last verified: 2010-11

Locations

CA (1); US (34); AU (5)