Clinical trial NCT00112359: International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Pseudomonas aeruginosa
Pulmonary Cystic Fibrosis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2005-06-02
Enrollment: 166
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in CFQ-R Respiratory Symptoms Scale (RSS) Score
timeFrame: Day 0 to Day 28
Secondary outcomes:
measure: Change in CFQ-R RSS Score
timeFrame: Day 0 to Day 14
measure: Change in CFQ-R RSS Score
timeFrame: Day 0 to Day 42
measure: Percent Change in FEV1 (L)
timeFrame: Day 0 to Day 28
measure: Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum
timeFrame: Day 0 to Day 28
measure: Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug
timeFrame: Day 0 to Day 42
measure: Number of Participants Hospitalized at Least Once Between Day 0 and Day 42
timeFrame: Day 0 to Day 42
Other outcomes:
measure: Number of Participants With Other Pathogens Present
timeFrame: Day 0 to Day 28
measure: Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL)
timeFrame: Day 0
measure: Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL)
timeFrame: Day 28
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Anchorage
country: United States
facility: Pediatric Breathing Disorders Clinic
state: Alaska
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital, Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: Capital Allergy and Respiratory Disease Center
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Health Sciences Center
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic, Orlando
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital / Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Wichita
country: United States
facility: Via Christi - St. Francis Regional Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Auburn
country: United States
facility: Central Maine Pulmonary Associates
state: Maine
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Las Vegas
country: United States
facility: Children's Lung Specialists
state: Nevada
city: Livingston
country: United States
facility: St. Barnabas Healthcare System
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Columbia
country: United States
facility: Pediatric Pulmonary Associates, South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor Martha Foster Lung Care Center
state: Texas
city: San Antonio
country: United States
facility: Alamo Clinical Research Associates
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Portsmouth
country: United States
facility: Naval Medical Center
state: Virginia
city: Richmond
country: United States
facility: Pediatric Pulmonary Center/Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Children's Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Prahran
country: Australia
facility: Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: Capital Health and the Governors of the University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: London
country: Canada
facility: Brian Lyttle Professional Corporation
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Auckland
country: New Zealand
facility: Auckland District Health Board
Study officials:
affiliation: Corus Pharma, Inc.
name: Bruce Montgomery, MD
role: STUDY_DIRECTOR
References:
citation: Retsch-Bogart GZ, Quittner AL, Gibson RL, Oermann CM, McCoy KS, Montgomery AB, Cooper PJ. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest. 2009 May;135(5):1223-1232. doi: 10.1378/chest.08-1421.