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

Cystic Fibrosis Clinical Trial

— AIR-CF1  

Official title:

A Phase 3, Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary Pseudomonas Aeruginosa (AIR-CF1)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112359
• Other study ID #: CP-AI-007
• Status: Completed
• Phase: Phase 3
• First received: June 1, 2005
• Last updated: March 21, 2011
• Start date: May 2005
• Est. completion date: April 2007

Study information

• Verified date: March 2011
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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) and lung infection due to Pseudomonas aeruginosa (PA).

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 TID using the PARI eFlow® electronic nebulizer, in CF patients with PA.

In this study, participant eligibility was assessed at a screening visit 7 to 14 days prior to the baseline visit (Day 0). Those participants who continued to meet eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI TID 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 study drug (Day 42).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• 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 greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);

• Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or

• Abnormal nasal potential difference.

• PA present in expectorated sputum or throat swab culture at Screening.

• FEV1 between (and including) 25% and 75% predicted at Screening.

• Negative pregnancy test at Screening.

• Ability to perform reproducible pulmonary function tests.

• Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.

• Ability to provide written informed consent.

Exclusion Criteria:

• Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening.

• Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day.

• History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years.

• History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.

• Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer).

• Known local or systemic hypersensitivity to monobactam antibiotics.

• Inability to tolerate short-acting bronchodilator use at least three times daily.

• Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit.

• Changes in physiotherapy technique or schedule within 7 days prior to 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 at Screening.

• 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.

• Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.

Study Design

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• AZLI 75 mg three times a day (TID)

• Placebo three times a day (TID)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Children's Hospital	Herston	Queensland
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Alfred Hospital	Prahran	Victoria
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Canada	Capital Health and the Governors of the University of Alberta	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Brian Lyttle Professional Corporation	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	St. Paul's Hospital	Vancouver	British Columbia
New Zealand	Auckland District Health Board	Auckland
United States	Albany Medical College	Albany	New York
United States	Pediatric Breathing Disorders Clinic	Anchorage	Alaska
United States	University of Michigan	Ann Arbor	Michigan
United States	Central Maine Pulmonary Associates	Auburn	Maine
United States	Medical College of Georgia	Augusta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Children's Memorial Hospital / Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Pediatric Pulmonary Associates, South Carolina	Columbia	South Carolina
United States	University of Missouri	Columbia	Missouri
United States	Baylor Martha Foster Lung Care Center	Dallas	Texas
United States	University of Florida Health Sciences Center	Gainesville	Florida
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Lung Specialists	Las Vegas	Nevada
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Barnabas Healthcare System	Livingston	New Jersey
United States	Miller Children's Hospital	Long Beach	California
United States	Children's Hospital, Los Angeles	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Children's Hospital of Orange County	Orange	California
United States	Nemours Children's Clinic, Orlando	Orlando	Florida
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Naval Medical Center	Portsmouth	Virginia
United States	Pediatric Pulmonary Center/Virginia Commonwealth University	Richmond	Virginia
United States	Capital Allergy and Respiratory Disease Center	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	Alamo Clinical Research Associates	San Antonio	Texas
United States	University of Washington Medical Center	Seattle	Washington
United States	Louisiana State University Health Sciences Center	Shreveport	Louisiana
United States	St. Louis University	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Via Christi - St. Francis Regional Medical Center	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CFQ-R Respiratory Symptoms Scale (RSS) Score	The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R respiratory symptoms scale (RSS; range of scores: 0-100; higher scores indicate fewer symptoms).	Day 0 to Day 28	No
Secondary	Change in CFQ-R RSS Score	The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).	Day 0 to Day 14	No
Secondary	Change in CFQ-R RSS Score	The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).	Day 0 to Day 42	No
Secondary	Percent Change in FEV1 (L)	Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. The percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was determined at Day 28.	Day 0 to Day 28	No
Secondary	Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum	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.	Day 0 to Day 28	No
Secondary	Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug	Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.	Day 0 to Day 42	No
Secondary	Number of Participants Hospitalized at Least Once Between Day 0 and Day 42	Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.	Day 0 to Day 42	No