Dual release ciprofloxacin for inhalation (DRCFI) reduces sputum pseudomonas aeruginosa ( Pa ) density and delays time to infective pulmonary exacerbation in non-cystic fibrosis (CF) bronchiectasis (BE)

Prior studies of inhaled therapies with proven efficacy in CF have failed to translate into beneficial treatments for non-CF BE and even suggested potential for harm. Novel, effective therapies for non-CF BE are urgently needed. DRCFI is a novel liposomal formulation which delivers the antibiotic in a controlled way resulting in an initial high peak of ciprofloxacin followed by prolonged high concentrations of the antibiotic in the lung. In this 24 week Phase 2 multicentre, double-blind trial, 42 BE subjects with chronic Pa infection were randomized to once daily inhaled DRCFI or matching inhaled placebo for three treatment cycles (28 days on, 28 days off). DRCFI resulted in a highly significant reduction in the primary outcome measure in sputum PA density at 28 days of 4.2 log 10 units in the DRCFI group, vs a decrease of 0.1 log 10 units in the placebo group. 17 subjects in the placebo group required supplemental antibiotics for respiratory-related infections versus 8 subjects in the DRCFI group (p=0.05). DRCFI demostrated a delay in the median time to first exacerbation of 58 days in the placebo group versus 134 days in the DRCFI group. In contrast to prior studies of nebulized antibiotics in this patient group, DRCFI was well tolerated overall. Fewer respiratory adverse events occurred in the DRCFI group compared to the placebo group and overall the incidence and severity of all other adverse events were similar. In subjects with non-CF BE, DRCFI is well tolerated, has a potent anti-Pseudomonal effect and significantly delays time to exacerbation. Supported by Aradigm Corporation.