Two phase 3 placebo-controlled trials of aztreonam lysine for inhalation (AZLI) for non-cystic fibrosis bronchiectasis (NCFB)

INTRODUCTION: We report the results of AIR-BX 1 and AIR-BX2, two randomized, double-blind, placebo-controlled international trials of AZLI in NCFB with 266 and 273 randomized subjects respectively. The primary endpoint was change in respiratory symptoms using a new, disease-specific health-related quality of life tool, Quality of Life-Bronchiectasis (QOL-B), following one course of therapy (ΔQOLB Day 28). Secondary endpoints were change in (ΔQOLB Day 84) after a second course of therapy and time to first protocol-defined exacerbation (PDE). METHODS: Subjects received 75 mg of AZLI TID or placebo via an eFlow nebulizer for two 28-day on/off cycles for a total of 112 days of observation. Inclusion criteria included confirmation of bronchiectasis by high resolution CT, presence of a target gram negative organism in sputum culture at screening and an FEV1 of ≥20% predicted. RESULTS: AIR-BX1 did not meet statistical significance for the primary endpoint of ΔQOLB at Day 28 (p=0.68) while AIR-BX2 did (p=0.011), although the magnitude of change relative to placebo was less than the minimal importance difference, calculated by anchor and distribution-based methods (7.8-9.3 points). Both studies failed to achieve a significant ΔQOLB at Day 84 and time to first PDE. AZLI treatment decreased bacterial burden in both studies. AEs and SAEs were more frequent in AZLI versus placebo arms in both studies, with a larger difference seen in AIR-BX1. CONCLUSIONS: AZLI did not provide significant clinical benefit in NCFB as measured by symptom score and time to PDE.