Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study

Abstract

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis.Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study.60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g−1 (range -9.78–5.02 log10 CFU·g−1)) compared with placebo (-0.27 log10 CFU·g−1 (range -7.96–5.25 log10 CFU·g−1)); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low.Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.

Management of bronchiectasis in adults

“…The phase II study showed excellent results with a significant reduction in P. aeruginosa CFU·mL −1 in the treatment arm (20 for ciprofloxacin versus 22 for placebo) over 24 weeks. There was also a reduction in time to next exacerbation (median 134 days versus 58 days; p=0.046 in the per protocol population) In contrast to the previous experience with aminoglycosides and aztreonam, however, both the dry powder and liposomal ciprofloxacin preparations were well tolerated [86,87]. The current evidence for inhaled antibiotics in bronchiectasis is summarised in table 2.…”

“…As of 2014, phase 3 trials of two formulations of inhaled ciprofloxacin have now commenced [86,87]. A dry powder inhaled formulation has the potential to significantly reduce treatment burden.…”

“…A dry powder inhaled formulation has the potential to significantly reduce treatment burden. In a phase II study (n=60 patients for ciprofloxacin and n=64 patients for placebo) ciprofloxacin was associated with a significant reduction in bacterial load during a 28-day treatment period, without any significant differences in exacerbations [86] These trials have included patients with both P. aeruginosa and other bacteria, while most other trials have limited their indication to patients with chronic P. aeruginosa [86]. This is the case for the dual release liposomal ciprofloxacin preparation.…”

Inhaled Antibiotics for Lower Airway Infections

“…A number of other inhaled antibiotics, such as nebulized liposomal amikacin, nebulized aztreonam lysine, and both nebulized (27) and dry powder forms (28) of ciprofloxacin, are being investigated in both phase 2 and 3 clinical trials in non-CF bronchiectasis (Table E2).…”

Inhaled antibiotics: dry or wet?

“…Similarly, a DPI for colistin (Colobreathe; Forest Laboratories Inc., New York, NY, USA) has also recently been developed [18,20]. Other antibiotics that are in development as DPI formulations are ciprofloxacin, levofloxacin, vancomycin and clarithromycin [21][22][23][24][25]. Regulatory studies of TIP and Colobreathe have shown noninferiority relative to the nebulised solutions.…”