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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01641822
First received: July 13, 2012
Last updated: April 6, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Cystic Fibrosis
Drug: AZLI
Drug: Placebo to match AZLI
Drug: Tobramycin inhalation solution
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24 [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
    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:
  • Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20) [ Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
  • Time to First Protocol-defined Pulmonary Exacerbation [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
    The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.

  • Rate of Hospitalizations for a Respiratory Event [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
    The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.

  • 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) [ Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20 ] [ Designated as safety issue: No ]
    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.


Enrollment: 107
Study Start Date: December 2012
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: AZLI
Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
Other Name: Cayston®
Drug: Tobramycin inhalation solution
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Other Name: TOBI®
Placebo Comparator: Placebo
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.
Drug: Placebo to match AZLI
Placebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer
Drug: Tobramycin inhalation solution
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Other Name: TOBI®

  Eligibility

Ages Eligible for Study:   6 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01641822

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
University of California - San Diego
La Jolla, California, United States, 92093
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Kaiser Permanente Medical Center
Oakland, California, United States, 94611
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington DC, District of Columbia, United States, 20010
United States, Florida
Central Florida Pulmonary Group
Altamonte Springs, Florida, United States, 32701
University of Florida
Gainesville, Florida, United States, 32610
South Broward Hospital dba Memorial Healthcare System
Hollywood, Florida, United States, 33021
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207
University of Miami
Miami, Florida, United States, 33136
Arnold Palmer Hospital for Children
Orlando, Florida, United States, 32806
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32801
Nemour's Children's Clinic
Pensacola, Florida, United States, 32504
All Children's Hospital
St. Petersburg, Florida, United States, 33701
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Georgia
Emory Cystic Fibrosis Center
Atlanta, Georgia, United States, 30084
Georgia Health
Augusta, Georgia, United States, 30912
United States, Idaho
St. Lukes Medical Center
Boise, Idaho, United States, 37012
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
Glenview, Illinois, United States, 60025
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maine
Maine Medical Center
Portland, Maine, United States, 38103
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Harper University Hospital
Detroit, Michigan, United States, 48201
Spectrum Health - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
St. Louis University - Cardinal Glennon Children's Hospital
St. Louis, Missouri, United States, 63104
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
Children's Lung Specialists
Las Vegas, Nevada, United States, 89107
United States, New Hampshire
Dartmouth Hitchcock Specialty Care Clinic
Bedford, New Hampshire, United States, 03110
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Morristown Medical Center
Morristown, New Jersey, United States, 07962
United States, New Mexico
UNM Clinical and Translational Center
Albuquerque, New Mexico, United States, 87131
United States, New York
Albany Medical College
Albany, New York, United States, 12208
Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
New Hyde Park, New York, United States, 11042
Gunnar Esiason Adult CF and Lung Program
New York, New York, United States, 10032
SUNY Upstate University
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
UC Health - University of Cincinnati
Cincinnati, Ohio, United States, 45267
The Toledo Hospital/Toledo Children's Hospital CF Center
Toledo, Ohio, United States, 43606
United States, Oklahoma
Santiago Reyes, MD
Oklahoma City, Oklahoma, United States, 73112
OU Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Geisinger Clinic
Danville, Pennsylvania, United States, 17822
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19107
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
University of Tennessee Medical Center
Knoxville, Tennessee, United States, 37920
Children's Foundation Research Institute/UTHSC
Memphis, Tennessee, United States, 28103
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232
United States, Texas
Austin Children's Chest Associates
Austin, Texas, United States, 78723
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Ft. Worth, Texas, United States, 76104
Alamo Clinical Research Associates
San Antonio, Texas, United States, 78212
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Vermont
Vermont Lung Center at the University of Vermont
Colchester, Vermont, United States, 05446
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23510
VCU Children's Hospital
Richmond, Virginia, United States, 23298
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53201
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Mark Bresnik, MD Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01641822     History of Changes
Other Study ID Numbers: GS-US-205-0170  2015-000398-11 
Study First Received: July 13, 2012
Results First Received: January 15, 2016
Last Updated: April 6, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pseudomonas Infections
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Gram-Negative Bacterial Infections
Bacterial Infections
Pharmaceutical Solutions
Tobramycin
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 26, 2016