Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study.

PURPOSE: To assess efficacy and safety of a new dry powder formulation of inhaled colistimethate sodium in patients with cystic fibrosis (CF) aged ≥6 years with chronic Pseudomonas aeruginosa lung infection. STUDY DESIGN AND METHODS: A prospective, centrally randomised, phase III, open-label study in patients with stable CF aged ≥6 years with chronic P aeruginosa lung infection. Patients were randomised to Colobreathe dry powder for inhalation (CDPI, one capsule containing colistimethate sodium 1 662 500 IU, twice daily) or three 28-day cycles with twice-daily 300 mg/5 ml tobramycin inhaler solution (TIS). Study duration was 24 weeks. RESULTS: 380 patients were randomised. After logarithmic transformation of data due to a non-normal distribution, adjusted mean difference between treatment groups (CDPI vs TIS) in change in forced expiratory volume in 1 s (FEV1% predicted) at week 24 was -0.98% (95% CI -2.74% to 0.86%) in the intention-to-treat population (n=373) and -0.56% (95% CI -2.71% to 1.70%) in the per protocol population (n=261). The proportion of colistin-resistant isolates in both groups was ≤1.1%. The number of adverse events was similar in both groups. Significantly more patients receiving CDPI rated their device as 'very easy or easy to use' (90.7% vs 53.9% respectively; p<0.001). CONCLUSION: CDPI demonstrated efficacy by virtue of non-inferiority to TIS in lung function after 24 weeks of treatment. There was no emergence of resistance of P aeruginosa to colistin. Overall, CDPI was well tolerated. TRIAL REG NO: EudraCT 2004-003675-36.