Article Text

Original article
Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial
  1. David J Serisier1,
  2. Diana Bilton2,
  3. Anthony De Soyza3,
  4. Philip J Thompson4,
  5. John Kolbe5,
  6. Hugh W Greville6,
  7. David Cipolla7,
  8. Paul Bruinenberg8,
  9. Igor Gonda7,
  10. the ORBIT-2 investigators
  1. 1Department of Respiratory Medicine, Mater Medical Research Institute and University of Queensland, Mater Adult Hospital, South Brisbane, Queensland, Australia
  2. 2Department of Respiratory Medicine, Royal Brompton Hospital, London, UK
  3. 3Adult Bronchiectasis Service, Institute of Cellular Medicine, Newcastle University and Freeman Hospital, Newcastle-upon-Tyne, UK
  4. 4Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia
  5. 5Respiratory Services, Auckland City Hospital and Department of Medicine, Faculty of Medical and Health Services, University of Auckland, Auckland, New Zealand
  6. 6Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  7. 7Aradigm Corporation, Hayward, California, USA
  8. 8Eagle Pharmaceuticals Inc, Woodcliff Lake, New Jersey, USA
  1. Correspondence to Dr David J Serisier, Department of Respiratory Medicine, Level 9 Mater Adult Hospital, Raymond Tce, South Brisbane, QLD 4101, Australia; david.serisier{at}mater.org.au

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.

  • Bronchiectasis
  • Respiratory Infection

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