title: Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected 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, placebo-controlled 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 ciprofloxacin-sensitive 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.
authors.affiliation: Department of Respiratory Medicine, Mater Medical Research Institute and University of Queensland, Mater Adult Hospital, South Brisbane, Queensland, Australia. david.serisier@mater.org.au
authors.forename: David J
authors.initials: DJ
authors.lastname: Serisier
authors.forename: Diana
authors.initials: D
authors.lastname: Bilton
authors.forename: Anthony
authors.initials: A
authors.lastname: De Soyza
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: John
authors.initials: J
authors.lastname: Kolbe
authors.forename: Hugh W
authors.initials: HW
authors.lastname: Greville
authors.forename: David
authors.initials: D
authors.lastname: Cipolla
authors.forename: Paul
authors.initials: P
authors.lastname: Bruinenberg
authors.forename: Igor
authors.initials: I
authors.lastname: Gonda
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001987:Bronchiectasis / Q000150:complications* / Q000382:microbiology; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa; D013183:Sputum / Q000382:microbiology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D002939:Ciprofloxacin
keywords: Bronchiectasis; Respiratory Infection