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Cystic fibrosis
Original article
Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection
  1. J P Clancy1,
  2. L Dupont2,
  3. M W Konstan3,
  4. J Billings4,
  5. S Fustik5,
  6. C H Goss6,
  7. J Lymp7,
  8. P Minic8,
  9. A L Quittner9,
  10. R C Rubenstein10,
  11. K R Young11,
  12. L Saiman12,
  13. J L Burns6,
  14. J R W Govan13,
  15. B Ramsey6,
  16. R Gupta14,
  17. for the Arikace Study Group
  1. 1Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  2. 2Department of Respiratory Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
  3. 3Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA
  4. 4Pulmonary, Allergy and Critical Care Division, University of Minnesota, Minneapolis, Minnesota, USA
  5. 5Department of Pediatrics, University Clinical Centre, Skopje, Macedonia
  6. 6Department of Medicine, University of Washington, Seattle, Washington, USA
  7. 7Seattle Children's Research Institute, Seattle, Washington, USA
  8. 8Department of Pulmonology, Institute for Mother and Child Healthcare, Belgrade, Serbia
  9. 9Department of Psychology, University of Miami, Miami, Florida, USA
  10. 10Division of Pulmonary Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
  11. 11Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA
  12. 12Department of Pediatrics, Columbia University, New York, New York, USA
  13. 13Department of Medical Microbiology, University of Edinburgh, Edinburgh, UK
  14. 14Department of Development, Insmed Incorporated, Monmouth Junction, New Jersey, USA
  1. Correspondence to Dr J P Clancy, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; john.clancy{at}cchmc.org

Abstract

Rationale Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition.

Objectives To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa.

Methods 105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV1)), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire—Revised (CFQ-R).

Results The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV1 was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs −0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV1 improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49).

Conclusions Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

  • Respiratory Infection
  • Cystic Fibrosis
  • Bacterial Infection

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

https://doi.org/10.1136/thoraxjnl-2012-202230

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