Abstract
The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa sputum density in patients with bronchiectasis.
This is a phase II, double-blind, randomised study in bronchiectasis patients aged ≥18 years with chronic P. aeruginosa infection. Patients were randomised 1:1:1 to either cohort A: three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (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.
Overall, 107 patients were randomised to cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the P. aeruginosa 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 bronchiectasis was the most frequent (37.4%) adverse event. Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to adverse events.
Continuous- and cyclical-TIP regimens with all three doses were safe and effective in reducing the P. aeruginosa sputum density in patients with bronchiectasis and chronic P. aeruginosa infection.
Abstract
Inhaled dry powder tobramycin (TOBI Podhaler) significantly reduced Pseudomonas aeruginosa sputum density and was well tolerated in patients with bronchiectasis https://bit.ly/3hsRQw9
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.03390-2020
This article has supplementary material available from erj.ersjournals.com
This study is registered at www.ClinicalTrials.gov with identifier number NCT02712983.
Data sharing provision has not been made for this study.
Elements of the information presented in this publication were presented at the 2020 American Thoracic Society Conference.
Conflict of interest: E. Polverino reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and personal fees from Bayer, Menarini, Grifols, Zambon, Pfizer, Chiesi, Teva, Shire, Insmed and Polyphor, and grants from Chiesi and Grifols, outside the submitted work.
Conflict of interest: J.D. Chalmers reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and 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: H.A.W.M. Tiddens reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and personal fees from Vertex and Gilead, grants and personal fees from Novartis, and grants from Roche, Vertex, Chiesi and Vectura, outside the submitted work.
Conflict of interest: H. Goossens reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study.
Conflict of interest: M. Tunney reports grants from European Union IMI grant in collaboration with Novartis, during the conduct of the study; and grants from European Union, Novartis and Alaxia SAS, outside the submitted work.
Conflict of interest: F.C. Ringhausen reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and 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: A.T. Hill reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study.
Conflict of interest: R. Pathan reports other from Novartis, outside the submitted work.
Conflict of interest: G. Angyalosi reports other from Novartis, outside the submitted work.
Conflict of interest: F. Blasi reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and 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: S.J. Elborn reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants from Novartis, and personal fees from Vertex, Galapagos and Ionis, outside the submitted work.
Conflict of interest: C.S. Haworth reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants and personal fees from Aradigm, Chiesi, Gilead, Grifols, GSK, Insmed, International Biophysics, Janssen, Mylan, Novartis, Teva, Vertex and Zambon, outside the submitted work.
Conflict of interest: M.R. Loebinger reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and personal fees from Bayer, Grifols, Astra Zeneca, Insmed and Polyphor, outside the submitted work.
Support statement: This work has received support from the European Union/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Joint Undertaking iABC grant agreement n°115721. The protocol was designed and conducted by Novartis in collaboration with the authors. Novartis was responsible for data collection, data analysis, data interpretation, and writing the article. All authors had full access to the entire study data and the corresponding author had the final responsibility for the decision to submit for publication. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received April 28, 2020.
- Accepted July 18, 2020.
- Copyright ©ERS 2021
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