Clinical trial NCT01641822: 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
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-07-17
Enrollment: 107
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24
timeFrame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Secondary outcomes:
measure: Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)
timeFrame: Comparative Phase: Baseline and Weeks 4, 12 and 20
measure: Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs
timeFrame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
measure: Time to First Protocol-defined Pulmonary Exacerbation
timeFrame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
measure: Rate of Hospitalizations for a Respiratory Event
timeFrame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
measure: 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)
timeFrame: Comparative Phase: Baseline and Weeks 4, 12 and 20
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Washington DC
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Altamonte Springs
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hollywood
country: United States
facility: South Broward Hospital dba Memorial Healthcare System
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic - Orlando
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Pensacola
country: United States
facility: Nemour's Children's Clinic
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Cystic Fibrosis Center
state: Georgia
city: Augusta
country: United States
facility: Georgia Health
state: Georgia
city: Boise
country: United States
facility: St. Lukes Medical Center
state: Idaho
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Glenview
country: United States
facility: Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health - Helen DeVos Children's Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: St. Louis
country: United States
facility: St. Louis University - Cardinal Glennon Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Children's Lung Specialists
state: Nevada
city: Bedford
country: United States
facility: Dartmouth Hitchcock Specialty Care Clinic
state: New Hampshire
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: UNM Clinical and Translational Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
state: New York
city: New York
country: United States
facility: Gunnar Esiason Adult CF and Lung Program
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: UC Health - University of Cincinnati
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital CF Center
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Sciences Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Santiago Reyes, MD
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Children's Foundation Research Institute/UTHSC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Austin
country: United States
facility: Austin Children's Chest Associates
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Ft. Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: San Antonio
country: United States
facility: Alamo Clinical Research Associates
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Colchester
country: United States
facility: Vermont Lung Center at the University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: VCU Children's Hospital
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Gilead Sciences
name: Mark Bresnik, MD
role: STUDY_DIRECTOR
References:
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.