112 Analysis of long-term use of liposomal amikacin for inhalation (LAI) in patients with cystic fibrosis (CF) who have chronic infection from Pseudomonas aeruginosa

Objective Interim analysis to evaluate safety, tolerability, and efficacy of LAI, a novel amikacin formulation, in CF patients with chronic P aeruginosa infection previously treated with LAI or tobramycin inhalation solution (TIS). Methods In the CLEAR-108 trial, patients were randomized 1:1 to 3 treatment cycles (28 days on/28 days off) of LAI 590 mg QD or TIS 300 mg BID via nebulizer, and stratified by age and forced expiratory volume in 1 second (FEV 1 ). Eligible patients completing the CLEAR-108 trial enrolled in CLEAR-110 for up to 12 treatment cycles of LAI 590 mg QD via nebulizer. Results Of 266 patients who completed CLEAR-108, 206 (92 LAI; 114 TIS) enrolled in CLEAR-110 and received at least 1 dose of LAI 590 mg QD. At this data cut, 149 patients had completed ≥1 year (6 cycles) of LAI treatment in CLEAR-110. At the end of the 6th off-treatment cycle, FEV 1 continued to improve above baseline; relative mean change was 1.11% and 3.39% in patients on prior TIS and LAI, respectively. P aeruginosa sputum density reductions were similar regardless of prior treatment. 84.5% of patients on LAI had ≥1 TEAE (mild, 23.8%; moderate, 49.0%). As in CLEAR-108, most AEs were respiratory: the highest frequency occurred in Cycle 1 for patients in CLEAR-110 from the TIS arm (Cycles 1, 6: 21.1%, 8.6%). In the LAI arm, respiratory AEs were 7.6% and 8.9% for Cycles 1 and 6. A complete 2-year data set is expected in 2015. Conclusion LAI provides sustained pulmonary function improvement in CF patients infected with P aeruginosa. LAI has stable safety/tolerability with prolonged exposure. Data from ongoing analyses will deepen understanding of factors impacting patient response.