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

Study Overview
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Brief Summary
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The AIR-BX1 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.

Official Title
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A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial Evaluating Repeated Courses of Aztreonam for Inhalation Solution in Subjects With Non-CF Bronchiectasis and Gram-Negative Endobronchial Infection

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: AZLI
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZLI-AZLI<br>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<br>* AZLI 75 mg reconstituted with diluent and administered via nebulizer three times daily<br>|
| Placebo Comparator: Placebo-AZLI<br>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<br>* AZLI 75 mg reconstituted with diluent and administered via nebulizer three times daily<br>Drug: Placebo<br>* Placebo to match AZLI administered via nebulizer three times daily<br>|

What is the study measuring?
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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 |