Background The delivery of antipseudomonal
antibiotics by inhalation to Pseudomonas aeruginosainfected subjects with non-cystic fibrosis (CF)
bronchiectasis is a logical extension of treatment
strategies successfully developed in CF bronchiectasis.
Dual release ciprofloxacin for inhalation (DRCFI) contains
liposomal ciprofloxacin, formulated to optimise airway
antibiotic delivery.
Methods Phase II, 24-week Australian/New Zealand
multicentre, randomised, double-blind, placebocontrolled trial in 42 adult bronchiectasis subjects with
≥2 pulmonary exacerbations in the prior 12 months and
ciprofloxacin-sensitive P aeruginosa at screening.
Subjects received DRCFI or placebo in three treatment
cycles of 28 days on/28 days off. The primary outcome
was change in sputum P aeruginosa bacterial density to
the end of treatment cycle 1 (day 28), analysed by
modified intention to treat (mITT). Key secondary
outcomes included safety and time to first pulmonary
exacerbation—after reaching the pulmonary exacerbation
endpoint subjects discontinued study drug although
remained in the study.
Results DRCFI resulted in a mean (SD) 4.2 (3.7) log10
CFU/g reduction in P aeruginosa bacterial density at day
28 (vs −0.08 (3.8) with placebo, p=0.002). DRCFI
treatment delayed time to first pulmonary exacerbation
(median 134 vs 58 days, p=0.057 mITT, p=0.046 per
protocol). DRCFI was well tolerated with a similar
incidence of systemic adverse events to the placebo
group, but fewer pulmonary adverse events.
Conclusions Once-daily inhaled DRCFI demonstrated
potent antipseudomonal microbiological efficacy in
adults with non-CF bronchiectasis and ciprofloxacinsensitive P aeruginosa. In this modest-sized phase II
study, DRCFI was also well tolerated and delayed time to
first pulmonary exacerbation in the per protocol
population.