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
AZLI CAT
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy (CAT) Regimen of Inhaled Antibiotics for the Treatment of Chronic Pulmonary Pseudomonas Aeruginosa Infection in Subjects With Cystic Fibrosis
2 other identifiers
interventional
107
1 country
71
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2012
71 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 13, 2012
CompletedFirst Posted
Study publicly available on registry
July 17, 2012
CompletedStudy Start
First participant enrolled
December 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2015
CompletedResults Posted
Study results publicly available
May 9, 2016
CompletedMay 9, 2016
April 1, 2016
2.1 years
July 13, 2012
January 15, 2016
April 6, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24
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.
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Secondary Outcomes (5)
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
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)
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)
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
Study Arms (2)
AZLI
ACTIVE COMPARATORParticipants 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 COMPARATORParticipants 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.
Interventions
Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
Placebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (71)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
University of California - San Diego
La Jolla, California, 92093, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Kaiser Permanente Medical Center
Oakland, California, 94611, United States
National Jewish Health
Denver, Colorado, 80206, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Central Florida Pulmonary Group
Altamonte Springs, Florida, 32701, United States
University of Florida
Gainesville, Florida, 32610, United States
South Broward Hospital dba Memorial Healthcare System
Hollywood, Florida, 33021, United States
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami
Miami, Florida, 33136, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, 32801, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemour's Children's Clinic
Pensacola, Florida, 32504, United States
All Children's Hospital
St. Petersburg, Florida, 33701, United States
Tampa General Hospital
Tampa, Florida, 33606, United States
Emory Cystic Fibrosis Center
Atlanta, Georgia, 30084, United States
Georgia Health
Augusta, Georgia, 30912, United States
St. Lukes Medical Center
Boise, Idaho, 37012, United States
University of Chicago
Chicago, Illinois, 60637, United States
Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
Glenview, Illinois, 60025, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Maine Medical Center
Portland, Maine, 38103, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Harper University Hospital
Detroit, Michigan, 48201, United States
Spectrum Health - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
St. Louis University - Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Children's Lung Specialists
Las Vegas, Nevada, 89107, United States
Dartmouth Hitchcock Specialty Care Clinic
Bedford, New Hampshire, 03110, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Morristown Medical Center
Morristown, New Jersey, 07962, United States
UNM Clinical and Translational Center
Albuquerque, New Mexico, 87131, United States
Albany Medical College
Albany, New York, 12208, United States
Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
New Hyde Park, New York, 11042, United States
Gunnar Esiason Adult CF and Lung Program
New York, New York, 10032, United States
SUNY Upstate University
Syracuse, New York, 13210, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Akron Children's Hospital
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229, United States
UC Health - University of Cincinnati
Cincinnati, Ohio, 45267, United States
The Toledo Hospital/Toledo Children's Hospital CF Center
Toledo, Ohio, 43606, United States
OU Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Santiago Reyes, MD
Oklahoma City, Oklahoma, 73112, United States
Geisinger Clinic
Danville, Pennsylvania, 17822, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19107, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
East Tennessee Children's Hospital
Knoxville, Tennessee, 37916, United States
University of Tennessee Medical Center
Knoxville, Tennessee, 37920, United States
Children's Foundation Research Institute/UTHSC
Memphis, Tennessee, 28103, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232, United States
Austin Children's Chest Associates
Austin, Texas, 78723, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Alamo Clinical Research Associates
San Antonio, Texas, 78212, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Vermont Lung Center at the University of Vermont
Colchester, Vermont, 05446, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23510, United States
VCU Children's Hospital
Richmond, Virginia, 23298, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53201, United States
Related Publications (1)
Flume PA, Clancy JP, Retsch-Bogart GZ, Tullis DE, Bresnik M, Derchak PA, Lewis SA, Ramsey BW. Continuous alternating inhaled antibiotics for chronic pseudomonal infection in cystic fibrosis. J Cyst Fibros. 2016 Nov;15(6):809-815. doi: 10.1016/j.jcf.2016.05.001. Epub 2016 May 24.
PMID: 27233377DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Mark Bresnik, MD
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 13, 2012
First Posted
July 17, 2012
Study Start
December 1, 2012
Primary Completion
January 1, 2015
Study Completion
January 1, 2015
Last Updated
May 9, 2016
Results First Posted
May 9, 2016
Record last verified: 2016-04