Interim data from a long-term safety, tolerability, and efficacy study of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonas aeruginosa infection

Rationale: Liposomal amikacin for inhalation (LAI) is a novel lipid formulation being developed to treat chronic Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients (pts). CLEAR-110 is an extension study of a completed LAI versus tobramycin inhalation solution comparator study (CLEAR-108) to evaluate long-term safety, tolerability, and efficacy of once-daily (QD) LAI. Methods : The study was conducted in 54 centers in 16 countries in Europe and Canada. Eligible pts from CLEAR-108 received LAI 590 mg QD via a PARI Investigational eFlow ® Nebulizer System (28 days on/off treatment) for 6 cycles (12 months) and could re-consent for additional 6 cycles (12 total [∼2 yrs]). Patients were evaluated every 28 days. Results: A total of 266 pts completed CLEAR-108; 206 (77%) enrolled in CLEAR-110 and received ≥1 dose of LAI. At the time of the interim data, 98 pts had completed 6 cycles of treatment. Overall, data show that LAI was well tolerated, and no unexpected adverse events (AEs) were observed. At the end of treatment of cycle 6, mean % increase from baseline in forced expiratory volume in 1 second (FEV1 [L]) was 3.65 % and 0.78% at the end of off-treatment period of the 6th cycle. Conclusion: These interim data demonstrate that LAI was well tolerated during 6 cycles, with AEs being consistent with those expected in a population of CF patients receiving inhaled medicines. Additionally, pts receiving 6 cycles of LAI showed mean increase in relative change in FEV1 that was sustained during both on- and off-treatment months, showing longer-term durability of treatment effect.