Phase 3 Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy Regimen for the Treatment of Chronic Pseudomonas Aeruginosa Infection in Patients With CF
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT01641822
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the safety and efficacy of a CAT regimen with aztreonam for inhalation solution (AZLI) and tobramycin inhalation solution (TIS) in adult and pediatric subjects with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection. Participants will be enrolled in a 28 day TIS run-in phase, and will be eligible for randomization in the comparative phase if they have not received non-study oral antibiotics for a respiratory event, or IV or inhaled antibiotics for any indication between Visits 2 and 3, have not developed a condition requiring hospitalization or other change in clinical status which, in the opinion of the investigator would preclude their ability to continue in the study, and have demonstrated at least 50% TIS compliance. Participants enrolled in the comparative phase will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI or placebo for 28 days followed by TIS for 28 days.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 107
- Confirmed diagnosis of CF
- Presence of PA in 2 lower respiratory tract cultures in the 12 months prior to screening
- Forced expiratory volume (FEV)1 ≥ 25 and ≤ 75% predicted
- History of 1 hospitalization or 1 course of IV antibiotics for an acute respiratory exacerbation in the 12 months prior to screening
- Concurrent use of oral, IV or inhaled antibiotics at enrollment
- Concurrent hospitalization at enrollment
- History of local or systemic hypersensitivity to monobactams or aminoglycoside antibiotics or history of aminoglycoside antibiotic associated toxicity
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Tobramycin inhalation solution Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS for 28 days. AZLI Tobramycin inhalation solution Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI for 28 days followed by TIS for 28 days. Placebo Placebo to match AZLI Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS for 28 days. AZLI AZLI Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI for 28 days followed by TIS for 28 days.
- Primary Outcome Measures
Name Time Method Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24 Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) PDEs were characterized by a change or worsening from baseline of 1 or more documented signs or symptoms (decreased exercise tolerance, increased cough, increased sputum or chest congestion, decreased appetite, or other signs or symptoms) associated with the use of non-study IV or inhaled antibiotics and be verified by a blinded independent adjudication committee.
- Secondary Outcome Measures
Name Time Method Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20) Comparative Phase: Baseline and Weeks 4, 12 and 20 FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex and body composition. The adjusted mean is from a mixed-effect model repeated measures (MMRM) analysis. The model includes terms for baseline value, previous exacerbations (1, 2, ≥ 3), treatment, visit (categorical), and treatment by visit interaction.
Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) Time to First Protocol-defined Pulmonary Exacerbation Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.
Average Change From Baseline in the CFQ-R Respiratory Symptom Scale (RSS) Score Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20) Comparative Phase: Baseline and Weeks 4, 12 and 20 Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS). The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms. The adjusted mean is from a mixed-effect model repeated measures (MMRM) analysis. The model includes terms for baseline value, previous exacerbations (1, 2, ≥ 3), treatment, visit (categorical), and treatment by visit interaction.
Rate of Hospitalizations for a Respiratory Event Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.
Related Research Topics
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Trial Locations
- Locations (71)
University of Chicago
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Children's Lung Specialists
🇺🇸Las Vegas, Nevada, United States
University of California - San Diego
🇺🇸La Jolla, California, United States
Kaiser Permanente Medical Center
🇺🇸Oakland, California, United States
Central Florida Pulmonary Group
🇺🇸Altamonte Springs, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
South Broward Hospital dba Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Nemour's Children's Clinic
🇺🇸Pensacola, Florida, United States
All Children's Hospital
🇺🇸St. Petersburg, Florida, United States
Emory Cystic Fibrosis Center
🇺🇸Atlanta, Georgia, United States
Georgia Health
🇺🇸Augusta, Georgia, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Spectrum Health - Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
St. Louis University - Cardinal Glennon Children's Hospital
🇺🇸St. Louis, Missouri, United States
Dartmouth Hitchcock Specialty Care Clinic
🇺🇸Bedford, New Hampshire, United States
UNM Clinical and Translational Center
🇺🇸Albuquerque, New Mexico, United States
Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
🇺🇸New Hyde Park, New York, United States
SUNY Upstate University
🇺🇸Syracuse, New York, United States
Gunnar Esiason Adult CF and Lung Program
🇺🇸New York, New York, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Geisinger Clinic
🇺🇸Danville, Pennsylvania, United States
The Toledo Hospital/Toledo Children's Hospital CF Center
🇺🇸Toledo, Ohio, United States
UC Health - University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Cook Children's Medical Center
🇺🇸Ft. Worth, Texas, United States
Vermont Lung Center at the University of Vermont
🇺🇸Colchester, Vermont, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Alamo Clinical Research Associates
🇺🇸San Antonio, Texas, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Harper University Hospital
🇺🇸Detroit, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
OU Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Santiago Reyes, MD
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
🇺🇸Glenview, Illinois, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Nemours Children's Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
St. Lukes Medical Center
🇺🇸Boise, Idaho, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's Foundation Research Institute/UTHSC
🇺🇸Memphis, Tennessee, United States
Children's National Medical Center
🇺🇸Washington DC, District of Columbia, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Albany Medical College
🇺🇸Albany, New York, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Austin Children's Chest Associates
🇺🇸Austin, Texas, United States
VCU Children's Hospital
🇺🇸Richmond, Virginia, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States