Multidose Safety and Tolerability Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKACE™)

A major factor in the respiratory health of cystic fibrosis (CF) subjects is acquisition of chronic Pseudomonas aeruginosa infections. The infection rate with P. aeruginosa increases with age and by age 18 years, 80% of CF subjects in the U.S. are infected. Liposomal Amikacin for Inhalation (Arikace™) is a sterile aqueous liposomal suspension consisting of amikacin sulfate encapsulated in liposomes. This formulation of amikacin maximizes the achievable dose and delivery to the lungs of subjects infected via a nebulizer. Because liposome particles are small enough to penetrate and diffuse through sputum into the bacterial biofilm, they deposit drug in close proximity to the bacterial colonies, thus improving the bioavailability of amikacin at the infection site. The clinically achievable doses of amikacin in the LAI formulation can effectively increase the half-life of the drug in the lungs, and decrease the potential for systemic toxicity. LAI offers several advantages over current therapies in treating CF subjects with chronic infection caused by P. aeruginosa.