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)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
AZLI
Placebo to match AZLI
Tobramycin inhalation solution
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham
- Phoenix Children's Hospital
- University of California - San Diego
- Children's Hospital Los Angeles
- Kaiser Permanente Medical Center
- National Jewish Health
- Alfred I. duPont Hospital for Children
- Children's National Medical Center
- Central Florida Pulmonary Group
- University of Florida
- South Broward Hospital dba Memorial Healthcare System
- Nemours Children's Clinic - Jacksonville
- University of Miami
- Nemours Children's Clinic - Orlando
- Arnold Palmer Hospital for Children
- Nemour's Children's Clinic
- All Children's Hospital
- Tampa General Hospital
- Emory Cystic Fibrosis Center
- Georgia Health
- St. Lukes Medical Center
- University of Chicago
- Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
- Indiana University
- Riley Hospital for Children
- University of Kansas Medical Center
- Maine Medical Center
- Boston Children's Hospital
- University of Michigan
- Harper University Hospital
- Spectrum Health - Helen DeVos Children's Hospital
- University of Mississippi Medical Center
- St. Louis University - Cardinal Glennon Children's Hospital
- University of Nebraska Medical Center
- Children's Lung Specialists
- Dartmouth Hitchcock Specialty Care Clinic
- Dartmouth Hitchcock Medical Center
- Morristown Medical Center
- UNM Clinical and Translational Center
- Albany Medical College
- Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
- Gunnar Esiason Adult CF and Lung Program
- SUNY Upstate University
- Duke University Medical Center
- Akron Children's Hospital
- Cincinnati Children's Hospital
- UC Health - University of Cincinnati
- The Toledo Hospital/Toledo Children's Hospital CF Center
- OU Health Sciences Center
- Santiago Reyes, MD
- Geisinger Clinic
- Penn State Milton S. Hershey Medical Center
- University of Pennsylvania
- Drexel University College of Medicine
- Children's Hospital of Pittsburgh
- Medical University of South Carolina
- East Tennessee Children's Hospital
- University of Tennessee Medical Center
- Children's Foundation Research Institute/UTHSC
- Vanderbilt Children's Hospital
- Austin Children's Chest Associates
- UT Southwestern Medical Center
- Cook Children's Medical Center
- Alamo Clinical Research Associates
- University of Utah
- Vermont Lung Center at the University of Vermont
- University of Virginia
- Children's Hospital of the King's Daughters
- VCU Children's Hospital
- West Virginia University
- Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
AZLI
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (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
Time to First Protocol-defined Pulmonary Exacerbation
The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.
Rate of Hospitalizations for a Respiratory Event
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01641822
Brief Title
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
Acronym
AZLI CAT
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZLI
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AZLI
Other Intervention Name(s)
Cayston®
Intervention Description
Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
Intervention Type
Drug
Intervention Name(s)
Placebo to match AZLI
Intervention Description
Placebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer
Intervention Type
Drug
Intervention Name(s)
Tobramycin inhalation solution
Other Intervention Name(s)
TOBI®
Intervention Description
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Primary Outcome Measure Information:
Title
Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24
Description
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.
Time Frame
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Secondary Outcome Measure Information:
Title
Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)
Description
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.
Time Frame
Comparative Phase: Baseline and Weeks 4, 12 and 20
Title
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)
Title
Time to First Protocol-defined Pulmonary Exacerbation
Description
The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.
Time Frame
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Title
Rate of Hospitalizations for a Respiratory Event
Description
The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.
Time Frame
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Title
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)
Description
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.
Time Frame
Comparative Phase: Baseline and Weeks 4, 12 and 20
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Bresnik, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
University of California - San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Kaiser Permanente Medical Center
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Alfred I. duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Children's National Medical Center
City
Washington DC
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Central Florida Pulmonary Group
City
Altamonte Springs
State/Province
Florida
ZIP/Postal Code
32701
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
South Broward Hospital dba Memorial Healthcare System
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Nemours Children's Clinic - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Nemours Children's Clinic - Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
Facility Name
Arnold Palmer Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Nemour's Children's Clinic
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
All Children's Hospital
City
St. Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Tampa General Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Emory Cystic Fibrosis Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30084
Country
United States
Facility Name
Georgia Health
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
St. Lukes Medical Center
City
Boise
State/Province
Idaho
ZIP/Postal Code
37012
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60025
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
38103
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Harper University Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Spectrum Health - Helen DeVos Children's Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
St. Louis University - Cardinal Glennon Children's Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Children's Lung Specialists
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89107
Country
United States
Facility Name
Dartmouth Hitchcock Specialty Care Clinic
City
Bedford
State/Province
New Hampshire
ZIP/Postal Code
03110
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
UNM Clinical and Translational Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Gunnar Esiason Adult CF and Lung Program
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
SUNY Upstate University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
UC Health - University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
The Toledo Hospital/Toledo Children's Hospital CF Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
OU Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Santiago Reyes, MD
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Geisinger Clinic
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Drexel University College of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
East Tennessee Children's Hospital
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37916
Country
United States
Facility Name
University of Tennessee Medical Center
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Children's Foundation Research Institute/UTHSC
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
28103
Country
United States
Facility Name
Vanderbilt Children's Hospital
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Austin Children's Chest Associates
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Cook Children's Medical Center
City
Ft. Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Alamo Clinical Research Associates
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78212
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Vermont Lung Center at the University of Vermont
City
Colchester
State/Province
Vermont
ZIP/Postal Code
05446
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
VCU Children's Hospital
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53201
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27233377
Citation
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.
Results Reference
derived
Learn more about this trial
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
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