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.
- Loebinger, M. R.
- Polverino, E.
- Chalmers, J. D.
- Tiddens, Hawm
- Goossens, H.
- Tunney, M.
- Ringshausen, F. C.
- Hill, A. T.
- Pathan, R.
- Angyalosi, G.
- Blasi, F.
- Elborn, S. J.
- Haworth, C. S.
Keywords
- Administration, Inhalation
- Adolescent
- Adult
- *Bronchiectasis/complications/drug therapy
- Humans
- *Pseudomonas Infections/complications/drug therapy
- Pseudomonas aeruginosa
- Tobramycin/therapeutic use
- 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.