Abstract
Introduction The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa (Pa) sputum density in patients with bronchiectasis (BE).
Methods This is a phase II, double-blind, randomised study in BE patients aged ≥18 years with chronic Pa infection. Patients were randomised 1:1:1 to either Cohort A: 3 capsules of TIP O.D. (84 mg); Cohort B: 5 capsules O.D. (140 mg) or Cohort C: 4 capsules B.I.D. (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP cyclically (alternating 28 days of TIP and placebo) or placebo for 16 weeks, respectively, and were followed up for 8 weeks.
Results Overall, 107 patients were randomised to Cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the Pa sputum density from baseline to Day 29 versus placebo in a dose-dependent manner (p≤0.0001, each). A smaller proportion of patients in the continuous-TIP (34.1%) and cyclical-TIP (35.7%) groups experienced pulmonary exacerbations versus placebo (47.6%) and also required fewer anti-pseudomonal antibiotics (38.6% on continuous-TIP and 42.9% on cyclical-TIP) versus placebo (57.1%) although not statistically significant. Pulmonary exacerbation of BE was the most frequent (37.4%) adverse event (AE). Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to AEs.
Conclusion Continuous- and cyclical-TIP regimens with all three doses were safe and effective in reducing the Pa sputum density in patients with BE and chronic Pa infection.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Loebinger reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; personal fees from Bayer, personal fees from Grifols, personal fees from Astra Zeneca, personal fees from Insmed, personal fees from Polyphor, outside the submitted work.
Conflict of interest: Dr. Polverino reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; personal fees from Bayer, personal fees from Menarini, personal fees from Grifols, personal fees from Zambon, personal fees from Pfizer, personal fees from Chiesi, personal fees from Teva, personal fees from Shire, personal fees from Insmed, personal fees from Polyphor, grants from Chiesi, grants from Grifols, outside the submitted work.
Conflict of interest: Dr. Chalmers reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; grants and personal fees from GSK, Boehringer-Ingelheim, AstraZeneca, Pfizer, Bayer Healthcare, Grifols, Napp, Aradigm corporation, and Insmed, outside the submitted work.
Conflict of interest: Dr. Tiddens reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; personal fees from Vertex, personal fees from Gilead, grants and personal fees from Novartis, grants from Roche, grants from Vertex, grants from Chiesi, grants from Vectura, outside the submitted work.
Conflict of interest: Dr. Goossens reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study.
Conflict of interest: Dr. Tunney reports grants from European Union IMI grant in collaboration with Novartis, during the conduct of the study; grants from European Union, Novartis, Alaxia SAS, outside the submitted work.
Conflict of interest: Dr. Ringshausen reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; grants, personal fees and non-financial support from Aposan, AstraZeneca, Bayer, Boehringer Ingelheim, Celtaxsys, Chiesi, Corbus, Grifols, InfectoPharm, Insmed, MSD, Novartis, PARI, Parion, Polyphor, Vertex and Zambon, outside the submitted work.
Conflict of interest: Dr. Hill reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study.
Conflict of interest: Dr. Pathan reports other from Novartis, outside the submitted work.
Conflict of interest: Dr. Angyalosi reports other from Novartis, outside the submitted work.
Conflict of interest: Dr. Blasi reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; grants and personal fees from AstraZeneca, Bayer, Grifols, Pfizer, Chiesi, GSK, Guidotti, Menarini, Novartis, Teva, Zambon and Insmed, outside the submitted work.
Conflict of interest: Dr. Elborn reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; grants from Novartis, personal fees from Vertex, personal fees from Galapagos, personal fees from Ionis, outside the submitted work.
Conflict of interest: Dr. Haworth reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; grants and personal fees from Aradigm, Chiesi, Gilead, Grifols, GSK, Insmed, International Biophysics, Janssen, Mylan, Novartis, Teva, Vertex and Zambon, outside the submitted work.
- Received April 28, 2020.
- Accepted July 18, 2020.
- Copyright ©ERS 2020
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