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 is currently recruiting participants.
Verified March 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01641822
First received: July 13, 2012
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This study is to investigate whether using a continuous alternating therapy (CAT) regimen of 2 antibiotics of different classes and with different mechanisms of action may provide the clinical benefits of reducing acute pulmonary exacerbations, maintaining lung function, and controlling respiratory symptoms for cystic fibrosis (CF) patients while minimizing the risk of emergence of antibiotic-resistant Pseudomonas aeruginosa (PA) strains.

After screening, eligible participants will be enrolled into the study and begin a 28-day run in period of tobramycin inhalation solution (TIS) twice daily. After the run-in, participants will return to the clinic and be randomized to either the Aztreonam for Inhalation Solution (AZLI) arm or the placebo arm. The AZLI arm has 3 cycles of AZLI three times daily for 28 days alternating with TIS twice daily for 28 days. The placebo arm has 3 cycles of placebo three times daily for 28 days alternating with 3 cycles of TIS twice daily for 28 days. Participants will return to the clinic for evaluation after each cycle of antibiotics for evaluation. There will be 9 scheduled study visits per participant.


Condition Intervention Phase
Cystic Fibrosis
Drug: Aztreonam for Inhalation Solution (AZLI)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 from baseline through Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Average actual change from baseline in forced expiratory volume in 1 second (FEV1) % predicted at the end of each course of study drug [ Time Frame: 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.

  • Time to first protocol-defined pulmonary exacerbation [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The time to first protocol-defined pulmonary exacerbation will be summarized using Kaplan-Meier (KM) summary statistics and analyzed using the log-rank test.

  • Rate of hospitalizations for a respiratory event [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The rate of respiratory hospitalizations will be summarized and analyzed using negative binomial regression methods similar to the primary endpoint analysis. Total number of events will also be presented.

  • Average change from baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Symptom Scale (RSS) score at the end of each course of study drug (Weeks 4, 12, and 20) [ Time Frame: Baseline to Weeks 4, 12, and 20 ] [ Designated as safety issue: No ]
  • Percent of subjects who use non-study IV or inhaled antibiotics for protocol-defined pulmonary exacerbations through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: November 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aztreonam for Inhalation Solution (AZLI) Drug: Aztreonam for Inhalation Solution (AZLI)
75 mg (1 ml) of aztreonam, supplied as Aztreonam for Inhalation Solution (AZLI) administered three times a day for 28 days per course.
Other Name: Cayston
Placebo Comparator: Sugar solution for inhalation Drug: Placebo
Sugar solution for inhalation administered three times a day for 28 days per course.

  Eligibility

Ages Eligible for Study:   6 Years and older
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
  • FEV1 ≥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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01641822

Contacts
Contact: Sheila Leitzinger 206 256-4904 sheila.leitzinger@gilead.com

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Principal Investigator: Wynton Hoover, MD         
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Principal Investigator: Peggy Radford, MD         
United States, California
University of California - San Diego Recruiting
La Jolla, California, United States, 92093
Principal Investigator: Kevin Shaw, MD         
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Principal Investigator: Thomas Keens, MD         
Kaiser Permanente Medical Center Recruiting
Oakland, California, United States, 94611
Principal Investigator: Greg Shay, MD         
United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Principal Investigator: David Nichols, MD         
United States, Delaware
Alfred I. duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Principal Investigator: Aaron Chidekel, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington DC, District of Columbia, United States, 20010
Principal Investigator: Iman Sami-Zakhari, MD         
United States, Florida
Central Florida Pulmonary Group Recruiting
Altamonte Springs, Florida, United States, 32701
Principal Investigator: Francisco Calimano, MD         
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Principal Investigator: Jorge Lascano, MD         
South Broward Hospital dba Memorial Healthcare System Recruiting
Hollywood, Florida, United States, 33021
Principal Investigator: Juan Martinez, MD         
Nemours Children's Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32207
Principal Investigator: David Schaeffer, MD         
University of Miami Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Matthias Salathe, MD         
Nemours Children's Clinic - Orlando Recruiting
Orlando, Florida, United States, 32801
Principal Investigator: Floyd Livingston, MD         
Arnold Palmer Hospital for Children Recruiting
Orlando, Florida, United States, 32806
Principal Investigator: Mark Weatherly, MD         
Nemour's Children's Clinic Recruiting
Pensacola, Florida, United States, 32504
Principal Investigator: Okan Elidemir, MD         
All Children's Hospital Recruiting
St. Petersburg, Florida, United States, 33701
Principal Investigator: Magdalyn Gondor, MD         
Tampa General Hospital Recruiting
Tampa, Florida, United States, 33606
Principal Investigator: Mark Rolfe, MD         
United States, Georgia
Emory Cystic Fibrosis Center Recruiting
Atlanta, Georgia, United States, 30084
Principal Investigator: Seth Walker, MD         
Georgia Health Recruiting
Augusta, Georgia, United States, 30912
Principal Investigator: Caralee Forseen, MD         
United States, Idaho
St. Lukes Medical Center Recruiting
Boise, Idaho, United States, 37012
Principal Investigator: Perry Brown, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Edward T Naureckas, MD         
Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure Recruiting
Glenview, Illinois, United States, 60025
Principal Investigator: Steven Boas, MD         
United States, Indiana
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Michelle Howenstine, MD         
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Michael Ober, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Principal Investigator: Joel Mermis, MD         
United States, Maine
Maine Medical Center Recruiting
Portland, Maine, United States, 38103
Principal Investigator: Ann Marie Cairns, DO         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Gregory Sawicki, MdD         
UMass Memorial Medical Center Withdrawn
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Samya Nasr, MD         
Harper University Hospital Recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Dana Kissner, MD         
Detroit Clinical Research Center Withdrawn
Farmington Hills, Michigan, United States, 48334
Spectrum Health - Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Principal Investigator: Susan Millard, MD         
United States, Mississippi
University of Mississippi Medical Center Recruiting
Jackson, Mississippi, United States, 39216
Principal Investigator: Joseph M Majure, MD         
United States, Missouri
St. Louis University - Cardinal Glennon Children's Hospital Recruiting
St. Louis, Missouri, United States, 63104
Principal Investigator: Gary M. Albers, MD         
Washington University Withdrawn
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Principal Investigator: John Colombo, MD         
United States, Nevada
Children's Lung Specialists Recruiting
Las Vegas, Nevada, United States, 89107
Principal Investigator: Craig Nakamura, MD         
United States, New Hampshire
Dartmouth Hitchcock Specialty Care Clinic Recruiting
Bedford, New Hampshire, United States, 03110
Principal Investigator: Pamela Hofley, MD         
Dartmouth Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Principal Investigator: Alix Ashare, MD         
United States, New Jersey
Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07962
Principal Investigator: Stanley Fiel, MD         
United States, New Mexico
UNM Clinical and Translational Center Recruiting
Albuquerque, New Mexico, United States, 87131
Principal Investigator: Hengameh Raissy, MD         
United States, New York
Albany Medical College Recruiting
Albany, New York, United States, 12208
Principal Investigator: Paul Comber, MD         
Women and Childrens Hospital of Buffalo Withdrawn
Buffalo, New York, United States, 14222
Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center Recruiting
New Hyde Park, New York, United States, 11042
Principal Investigator: Rubin Cohen, MD         
Gunnar Esiason Adult CF and Lung Program Recruiting
New York, New York, United States, 10032
Principal Investigator: Claire Keating, MD         
SUNY Upstate University Recruiting
Syracuse, New York, United States, 13210
Principal Investigator: James Sexton, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: Deanna Green, MD         
United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
Principal Investigator: Kimberly A. McBennett, MD, PhD         
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Principal Investigator: John Clancy, MD         
UC Health - University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Principal Investigator: Patricia Joseph, MD         
The Toledo Hospital/Toledo Children's Hospital CF Center Recruiting
Toledo, Ohio, United States, 43606
Principal Investigator: Pierre Vauthy, MD         
United States, Oklahoma
Santiago Reyes, MD Recruiting
Oklahoma City, Oklahoma, United States, 73112
Principal Investigator: Santiago Reyes, MD         
OU Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Principal Investigator: James Royall, MD         
United States, Pennsylvania
Geisinger Clinic Not yet recruiting
Danville, Pennsylvania, United States, 17822
Principal Investigator: Jason Stamm, MD         
Penn State Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Principal Investigator: Gavin Graff, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Daniel Dorgan, MD         
Drexel University College of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19107
Principal Investigator: Michael Stephen, MD         
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Principal Investigator: Jonathan Spahr, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Principal Investigator: Patrick Flume, MD         
United States, Tennessee
University of Tennessee Medical Center Recruiting
Knoxville, Tennessee, United States, 37920
Principal Investigator: Bruce Ludwig, MD         
East Tennessee Children's Hospital Recruiting
Knoxville, Tennessee, United States, 37916
Principal Investigator: John Rogers, MD         
Children's Foundation Research Institute/UTHSC Recruiting
Memphis, Tennessee, United States, 28103
Principal Investigator: Saumini Srinivasan, MD         
Vanderbilt Children's Hospital Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Rebekah Brown, MD         
United States, Texas
Austin Children's Chest Associates Recruiting
Austin, Texas, United States, 78723
Principal Investigator: Bennie McWilliams, MD         
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Raksha Jain, MD         
Cook Children's Medical Center Recruiting
Ft. Worth, Texas, United States, 76104
Principal Investigator: Maynard Dyson, MD         
Alamo Clinical Research Associates Recruiting
San Antonio, Texas, United States, 78212
Principal Investigator: Pedro Sepulveda, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Principal Investigator: Theodore Liou, MD         
United States, Vermont
Vermont Lung Center at the University of Vermont Recruiting
Colchester, Vermont, United States, 05446
Principal Investigator: Laurie Whittaker-LeClair, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Principal Investigator: Cynthia Brown, MD         
Children's Hospital of the King's Daughters Recruiting
Norfolk, Virginia, United States, 23510
Principal Investigator: Laura Sass, MD         
VCU Children's Hospital Recruiting
Richmond, Virginia, United States, 23298
Principal Investigator: Howard J Schmidt, MD         
United States, West Virginia
West Virginia University Recruiting
Morgantown, West Virginia, United States, 26506
Principal Investigator: Kathryn Moffett, MD         
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53201
Principal Investigator: Diana Quintero, MD         
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01641822     History of Changes
Other Study ID Numbers: GS-US-205-0170
Study First Received: July 13, 2012
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 17, 2014