Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis (AIR-BX2)

A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial Evaluating Repeated Courses of Aztreonam for Inhalation Solution/Aztreonam 75 mg Powder and Solvent for Nebuliser Solution in Subjects With Non-CF Bronchiectasis and Gram-Negative Endobronchial Infection (AIR-BX2)

The AIR-BX2 study enrolled people with non-cystic fibrosis (non-CF) bronchiectasis and gram-negative airway infection. Participants received two 28-day courses of either Aztreonam for Inhalation Solution (AZLI) or placebo taken 3 times a day. Each course was followed by a 28-day off-drug period. Following the two blinded courses, all participants received a 28-day course of open-label AZLI then were followed for an additional 56 days.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Drug: AZLI; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Perth, New South Wales, Australia, 6000
      • Royal Perth Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Daw Park, South Australia, Australia, 5041
      • Repatriation General Hospital
    • Toorak Gardens, South Australia, Australia, 5065
      • Burnside War Memorial Hospital Pharmacy
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Brussels, Belgium, 1070
    • CUB Hôpital Erasme
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Leuven, Belgium, 3000
    • KUL UZ Gasthuisberg
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1W 1V3
      • Kelowna Respiratory Research and Allergy Clinic
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • The Lung Centre at Vancouver General Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
• France
  • Gap, PACA, France, 05007 Cedex
    • CHICAS - Centre Hospitalier Intercommunal des Alpes du sud, site de GAP
  • Marseille, France, 13015
    • Service Activite Ambulatoire Pole Cardiovasculaire Hopital Nord
  • Montpellier Cedex 05, France, 34295
    • CHU de Montpellier-Hopital Arnaud de Villeneuve
  • Nice, France, 6002
    • Hôpital Pasteur, CHU de Nice
  • Pessac, France, 33604
    • Hôpital Haut-Lévêque
  • Toulouse, France, 31054 cedex 9
    • CHU Toulouse - Hôpital Larrey
• Germany
  • Berlin, Germany, 12200
    • Charité Campus Virchow-Klinikum
  • Berlin-Charlottenburg (Westend), Germany, 14052
    • Research Center for Medical Studies (RCMS)
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Giessen, Germany, 35392
    • University Hospital Gießen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes
  • Jena, Germany, 07747
    • Universitätsklinikum Jena Clinic for Internal Medicine II
  • Leipzig, Germany, 04357
    • POIS Leipzig GbR
  • Leipzig, Germany, 04103
    • Univ.-Klinikum Leipzig, Innere Med.
  • Munich, Germany, 80336
    • Klinikum Innenstadt der LMU Munchen
• Italy
  • Ferrara, Italy, 44121
    • S.Anna Hospital, University of Ferrara
  • Milan, Italy, 20122
    • UO Broncopneumologia IRCCS Fondazione Cà Granda Milano
  • Modena, Italy, 41100
    • University of Modena and Reggio Emilia
  • Naples, Italy, 80131
    • Azienda Universitaria Federico II
  • Pisa, Italy, 56124
    • Università di Pisa - Ospedale Cisanello
  • Verona, Italy, 37124
    • Ospendale Civile Maggiore Centro Regionale Fibrosi Cistica
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Medisch Centrum Alkmaar
  • Rotterdam, Netherlands, 3015GD
    • Erasmus MC
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08035
    • Hospital Vall D´Hebron
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Girona, Spain, 17007
    • Hospital Josep Trueta
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valencia, Spain, 46009
    • Hospital La Fe
• United Kingdom
  • Cambridgeshire, United Kingdom, CB23 3RE
    • Papworth Hospital NHS Trust
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Exeter, United Kingdom, EX5 5AN
    • Royal Devon and Exeter Hospital, NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Sir William Leech Centre for Lung Research, Freeman Hospital
  • Sheffield, United Kingdom, 532 1DA
    • GBS RE Sheffield Teaching Hospitals NHS Foundation Trust
  • Torquay, Devon, United Kingdom, TQ2 7AA
    • Torbay District General Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • Royal Wolverhampton Hospitals NHS Trust
• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Florence Research Associates
  • Arizona
    • Flagstaff, Arizona, United States, 86001
      • Clinical Trials Connection
    • Peoria, Arizona, United States, 85381
      • Phoenix Medical Group
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates
    • Scottsdale, Arizona, United States, 85258
      • AZ Pulmonary Specialists, Ltd
  • California
    • Orange, California, United States, 92780
      • Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital - Clinical Research Center
    • St. Petersburg, Florida, United States, 33707
      • Pasadena Center for Medical Research
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital - New Lung Associates
    • Winter Park, Florida, United States, 32789
      • Florida Premier Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Southeastern Lung Care PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Loess Hills Clinical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
  • Maryland
    • Rosedale, Maryland, United States, 21237
      • Pulmonary & Critical Care Associates of Baltimore
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson Medical School
    • Summit, New Jersey, United States, 07901
      • Pulmonary & Allergy Associates, P.A.
  • New York
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • New York, New York, United States, 10032
      • Columbia University, NY Presbyterian Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97220
      • The Oregon Clinic P.C./ Pulmonary Division
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center
  • Texas
    • Tyler, Texas, United States, 75708
      • University of Texas Health Science Center at Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Tacoma, Washington, United States, 98405
      • Pulmonary Consultants, PLLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male/Female 18 years or older with non-CF bronchiectasis
• Chronic sputum production on most days
• Positive sputum culture for gram-negative organisms
• Must have met lung function requirements

Exclusion Criteria:

• History of CF
• Hospitalized within 14 days prior to joining the study
• Previous exposure to AZLI
• Pregnant, breastfeeding, or unwilling to follow contraceptive measures for the study
• Must have met liver and kidney function requirements
• Continuous oxygen use of greater than 2 liters per minute (supplemental oxygen with activity and at night was allowed)
• Treatment for nontuberculous mycobacteria infection or active mycobacterium tuberculosis infection within 1 year of enrollment
• Other serious medical conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZLI-AZLI; Participants were randomized to receive blinded AZLI for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI for 28 days plus 56 days of treatment-free follow-up.	Drug: AZLI; AZLI 75 mg reconstituted with diluent and administered via nebulizer three times daily
Placebo Comparator: Placebo-AZLI; Participants were randomized to receive blinded placebo to match AZLI for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI for 28 days plus 56 days of treatment-free follow-up.	Drug: AZLI; AZLI 75 mg reconstituted with diluent and administered via nebulizer three times daily; Drug: Placebo; Placebo to match AZLI administered via nebulizer three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QOL-B Respiratory Symptoms Score at Day 28	The mean (SD) change in the Respiratory Symptoms score on the Quality of Life Questionnaire-Bronchiectasis (QOL-B) was measured from baseline to the end of Course 1 (Day 28). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.	Baseline to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QOL-B Respiratory Symptoms Score at Day 84	The mean (SD) change in the Respiratory Symptoms score on the QOL-B was measured from baseline to the end of Course 2 (Day 84). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.	Baseline to Day 84
Time to Protocol-Defined Exacerbation (PDE)	Protocol-defined exacerbation was defined as an acute worsening of respiratory disease that triggered the initiation of a non-study antibiotic meeting at least 3 major criteria, or 2 major and at least 2 minor criteria.; Major Criteria: increased sputum production; increased discoloration of sputum; increased dyspnea; increased cough; Minor Criteria: fever (> 38º C) measured during clinic visit; increased malaise or fatigue; forced expiratory volume in 1 second (FEV1) (L) or forced vital capacity (FVC) decreased > 10% from baseline; new or increased hemoptysis	Baseline to Day 112

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Principal Investigator: Anne O'Donnell, MD, Georgetown University Hospital

Publications and helpful links

General Publications

• Barker AF, O'Donnell AE, Flume P, Thompson PJ, Ruzi JD, de Gracia J, Boersma WG, De Soyza A, Shao L, Zhang J, Haas L, Lewis SA, Leitzinger S, Montgomery AB, McKevitt MT, Gossage D, Quittner AL, O'Riordan TG. Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med. 2014 Sep;2(9):738-49. doi: 10.1016/S2213-2600(14)70165-1. Epub 2014 Aug 18.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: March 11, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Estimate): April 16, 2014
• Last Update Submitted That Met QC Criteria: March 7, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: GS-US-219-0104