A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection.

Author(s): Retsch-Bogart GZ, Burns JL, Otto KL, Liou TG, McCoy K, Oermann C, Gibson RL, AZLI Phase II Study GroupJames Chmiel, MD and Cheryl Velotta, Rainbow Babies and Children's Hospital, Cleveland, OH; Karen McCoy, MD and Terri Johnson, Children's Hospital, Columbus, OH; Jeff Wagener, MD and Churee Penvari, The Children's Hospital, Denver, CO; Chris Oermann, MD and Charley Sellers, Texas Children's Hospital, Houston, TX; Marlyn Woo, MD and Lynn Fukushima, Children's Hospital Los Angeles, Los Angeles, CA; Marzena Krawiec, MD and Cindy Moodie, University of Wisconsin Hospital and

Affiliation(s): Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Publication date & source: 2008-01, Pediatr Pulmonol., 43(1):47-58.

Publication type:

BACKGROUND: Aztreonam lysine for inhalation (AZLI) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection. METHODS: This double-blind, randomized, placebo-controlled Phase 2 study evaluated the safety, tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow(R) Electronic Nebulizer (Pari Innovative Manufacturers, Inc., Midlothian, VA). Patients were 13 years and older with FEV(1) >/= 40% predicted, chronic P. aeruginosa infection, and had used no anti-pseudomonal antibiotics for 56 days. RESULTS: Of 131 patients screened, 105 received AZLI or placebo. Mean age was 26 years and mean FEV(1) percent predicted was 77% at baseline. There was a statistically significant reduction, compared to placebo, in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 (P < 0.001). The planned primary analysis, percent change in FEV(1) at Day 14, demonstrated no statistically significant difference. Post hoc analysis demonstrated significant increase in FEV(1) at Day 7 for the subset of patients with baseline FEV(1) < 75% predicted in the 225 mg AZLI group. Bronchodilator use was associated with greater improvement in FEV(1), as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group. Adverse events were similar between placebo and AZLI although there was a trend toward increased respiratory symptoms in the 225 mg AZLI group. CONCLUSION: These data support the further development of AZLI and provide information for the design of subsequent studies. Pediatr Pulmonol. 2008; 43:47-58. (c) 2007 Wiley-Liss, Inc.