International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: Placebo three times a day (TID)Drug: AZLI 75 mg three times a day (TID)
- Registration Number
- NCT00112359
- Lead Sponsor
- Gilead Sciences
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 166
-
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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo three times a day (TID) Placebo three times a day (TID) - AZLI 75 mg three times a day (TID) AZLI 75 mg three times a day (TID) -
- Primary Outcome Measures
Name Time Method Change in CFQ-R Respiratory Symptoms Scale (RSS) Score Day 0 to Day 28 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).
- Secondary Outcome Measures
Name Time Method Change in CFQ-R RSS Score Day 0 to Day 42 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).
Percent Change in FEV1 (L) Day 0 to Day 28 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.
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum Day 0 to Day 28 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.
Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug Day 0 to Day 42 Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.
Number of Participants Hospitalized at Least Once Between Day 0 and Day 42 Day 0 to Day 42 Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.
Trial Locations
- Locations (53)
Children's Memorial Hospital / Northwestern University
🇺🇸Chicago, Illinois, United States
University of Missouri
🇺🇸Columbia, Missouri, United States
University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Via Christi - St. Francis Regional Medical Center
🇺🇸Wichita, Kansas, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Central Maine Pulmonary Associates
🇺🇸Auburn, Maine, United States
Louisiana State University Health Sciences Center
🇺🇸Shreveport, Louisiana, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Capital Health and the Governors of the University of Alberta
🇨🇦Edmonton, Alberta, Canada
Albany Medical College
🇺🇸Albany, New York, United States
Pediatric Breathing Disorders Clinic
🇺🇸Anchorage, Alaska, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
St. Barnabas Healthcare System
🇺🇸Livingston, New Jersey, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Centre Hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montreal, Quebec, Canada
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Pediatric Pulmonary Associates, South Carolina
🇺🇸Columbia, South Carolina, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's Lung Specialists
🇺🇸Las Vegas, Nevada, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Miller Children's Hospital
🇺🇸Long Beach, California, United States
Children's Hospital, Los Angeles
🇺🇸Los Angeles, California, United States
Capital Allergy and Respiratory Disease Center
🇺🇸Sacramento, California, United States
Medical College of Georgia
🇺🇸Augusta, Georgia, United States
University of Florida Health Sciences Center
🇺🇸Gainesville, Florida, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Nemours Children's Clinic, Orlando
🇺🇸Orlando, Florida, United States
St. Louis University
🇺🇸St. Louis, Missouri, United States
Royal Children's Hospital
🇦🇺Herston, Queensland, Australia
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Brian Lyttle Professional Corporation
🇨🇦London, Ontario, Canada
Auckland District Health Board
🇳🇿Auckland, New Zealand
Baylor Martha Foster Lung Care Center
🇺🇸Dallas, Texas, United States
Naval Medical Center
🇺🇸Portsmouth, Virginia, United States
Alamo Clinical Research Associates
🇺🇸San Antonio, Texas, United States
Pediatric Pulmonary Center/Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Alfred Hospital
🇦🇺Prahran, Victoria, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada