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

Cystic Fibrosis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01641822
• Other study ID #: GS-US-205-0170
• Status: Completed
• Phase: Phase 3
• First received: July 13, 2012
• Last updated: April 9, 2015
• Start date: November 2012
• Est. completion date: January 2015

Study information

• Verified date: April 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pseudomonas Infections

Intervention

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.
• Placebo
Sugar solution for inhalation administered three times a day for 28 days per course.

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	UNM Clinical and Translational Center	Albuquerque	New Mexico
United States	Central Florida Pulmonary Group	Altamonte Springs	Florida
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Cystic Fibrosis Center	Atlanta	Georgia
United States	Georgia Health	Augusta	Georgia
United States	Austin Children's Chest Associates	Austin	Texas
United States	Dartmouth Hitchcock Specialty Care Clinic	Bedford	New Hampshire
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Lukes Medical Center	Boise	Idaho
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	UC Health - University of Cincinnati	Cincinnati	Ohio
United States	Vermont Lung Center at the University of Vermont	Colchester	Vermont
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Geisinger Clinic	Danville	Pennsylvania
United States	National Jewish Health	Denver	Colorado
United States	Harper University Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Ft. Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure	Glenview	Illinois
United States	Spectrum Health - Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	South Broward Hospital dba Memorial Healthcare System	Hollywood	Florida
United States	Indiana University	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University of California - San Diego	La Jolla	California
United States	Children's Lung Specialists	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Children's Foundation Research Institute/UTHSC	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center	New Hyde Park	New York
United States	Gunnar Esiason Adult CF and Lung Program	New York	New York
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Kaiser Permanente Medical Center	Oakland	California
United States	OU Health Sciences Center	Oklahoma City	Oklahoma
United States	Santiago Reyes, MD	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Nemour's Children's Clinic	Pensacola	Florida
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	VCU Children's Hospital	Richmond	Virginia
United States	University of Utah	Salt Lake City	Utah
United States	Alamo Clinical Research Associates	San Antonio	Texas
United States	St. Louis University - Cardinal Glennon Children's Hospital	St. Louis	Missouri
United States	All Children's Hospital	St. Petersburg	Florida
United States	SUNY Upstate University	Syracuse	New York
United States	Tampa General Hospital	Tampa	Florida
United States	The Toledo Hospital/Toledo Children's Hospital CF Center	Toledo	Ohio
United States	Children's National Medical Center	Washington DC	District of Columbia
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of protocol-defined exacerbations from baseline through Week 24		24 weeks	No
Secondary	Average actual change from baseline in forced expiratory volume in 1 second (FEV1) % predicted at the end of each course of study drug	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.	Weeks 4, 12 and 20	No
Secondary	Time to first protocol-defined pulmonary exacerbation	The time to first protocol-defined pulmonary exacerbation will be summarized using Kaplan-Meier (KM) summary statistics and analyzed using the log-rank test.	Baseline to Week 24	No
Secondary	Rate of hospitalizations for a respiratory event	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.	Baseline to Week 24	No
Secondary	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)		Baseline to Weeks 4, 12, and 20	No
Secondary	Percent of subjects who use non-study IV or inhaled antibiotics for protocol-defined pulmonary exacerbations through Week 24		Baseline to Week 24	No