Efficacy and safety of TOBI Podhaler® in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study

Michael R. Loebinger (Lead / Corresponding author), Eva Polverino, James D. Chalmers, Harm A. W. M. Tiddens, Herman Goossens, Felix C. Ringhausen, Michael Tunney, Adam T. Hill, Rashidkhan Pathan, Gerhild Angyalosi, Francesco Blasi, Stuart J. Elborn, Charles S. Haworth,

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalEuropean Respiratory Journal
Early online date27 Aug 2020
DOIs
Publication statusE-pub ahead of print - 27 Aug 2020

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    Loebinger, M. R., Polverino, E., Chalmers, J. D., Tiddens, H. A. W. M., Goossens, H., Ringhausen, F. C., Tunney, M., Hill, A. T., Pathan, R., Angyalosi, G., Blasi, F., Elborn, S. J., Haworth, C. S. (2020). Efficacy and safety of TOBI Podhaler® in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study. European Respiratory Journal. https://doi.org/10.1183/13993003.01451-2020