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

• ClinicalTrials.gov Identifier: NCT01314716
• Recruitment Status: Completed
• First Posted: March 14, 2011
• Results First Posted: April 16, 2014
• Last Update Posted: April 16, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: March 11, 2011
• First Posted Date: March 14, 2011
• Results First Submitted Date: March 7, 2014
• Results First Posted Date: April 16, 2014
• Last Update Posted Date: April 16, 2014
• Study Start Date: April 2011
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2014)

Change in QOL-B Respiratory Symptoms Score at Day 28 [ Time Frame: Baseline to 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.

Original Primary Outcome Measures (submitted: March 11, 2011)

Change in QOL-B Respiratory Symptoms Score [ Time Frame: Baseline to end of treatment course 1 (Day 28) ]

Change in the Respiratory Symptoms score on the Quality of Life Questionaire-Bronchiectasis(QOL-B) from baseline to the end of the placebo-controlled course 1 treatment with AZLI or placebo (Day 28)

Current Secondary Outcome Measures (submitted: March 7, 2014)

• Change in QOL-B Respiratory Symptoms Score at Day 84 [ Time Frame: Baseline to 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.
• Time to Protocol-Defined Exacerbation (PDE) [ Time Frame: Baseline to Day 112 ]
  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

Original Secondary Outcome Measures (submitted: March 11, 2011)

• Change in QOL-B Respiratory Symptoms and Physical Functioning Scores [ Time Frame: Baseline to end of treatment course 1 and 2. ]
• Time to Exacerbation [ Time Frame: From baseline to open label treatment (4 months) ]
  Time to protocol defined exacerbation prior to open-label AZLI treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Bronchiectasis

Intervention

• 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

Study Arms

• 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.
  Intervention: Drug: AZLI
• 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.
  Interventions:

  • Drug: AZLI
  • Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2013): 274
• Original Estimated Enrollment (submitted: March 11, 2011): 172
• Actual Study Completion Date: July 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT01314716
• Other Study ID Numbers: GS-US-219-0104
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Principal Investigator: Anne O'Donnell, MD; Georgetown University Hospital

• PRS Account: Gilead Sciences
• Verification Date: March 2014