118 Efficacy and safety of colistimethate sodium in a paediatric population: Results from the FREEDOM trial

Abstract

Objectives Colistimethate sodium is approved for the management of chronic pulmonary Pseudomonas aeruginosa (PA) infection in patients with cystic fibrosis (CF) ≥6 years. We aimed to compare the efficacy and safety of colistimethate dry powder inhaler (CMS DPI) to tobramycin nebulizer solution in paediatric patients with CF and chronic PA infection. Methods In this 24-week, phase-3, open label, active-controlled study, patients ≥6 years with forced expiratory volume in 1 second (FEV 1 ) 25–75% predicted were randomized 1:1 to twice-daily CMS DPI 125 mg (continuous therapy) or nebulized tobramycin 300 mg (three consecutive 28-day on-off cycles). The primary outcome – change from baseline in FEV 1 % predicted at week 24 – was analyzed in paediatric patient subgroups (6–12 y or 13–17 y). Antibiotic sensitivity testing and adverse events (AEs) monitoring were conducted. Results Of 154 paediatric patients included in the intention-to-treat population, 72 received CMS DPI. At week 24, adjusted differences (95% CI) in FEV 1 % predicted were 0.26 (–5.96, 6.47) and –3.04 (–8.96, 2.89) for patients aged 6–12 y and 13–17 y. While the overall incidence of colistin-resistant isolates was low in paediatric patients, there was a notable increase in the percentage of tobramycin-resistant isolates in patients 6–12 y. The occurrence of AEs, SAEs, and discontinuations due to AEs were similar between treatment groups. Conclusion In pediatric patients with CF and chronic pulmonary PA infection, the efficacy of colistimethate DPI was similar to nebulized tobramycin, but without antibiotic resistance. Colistimethate was well tolerated, and data suggest that CMS DPI can be safely administered to pediatric patients.