TY - JOUR
T1 - Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection
T2 - Design of a dose-finding study (iBEST-1)
AU - Loebinger, Michael R.
AU - Polverino, Eva
AU - Blasi, Francesco
AU - Elborn, Stuart J.
AU - Chalmers, James D.
AU - Goossens, Herman
AU - Tiddens, Harm Awm
AU - Tunney, Michael
AU - Zhou, Wenchun
AU - Angyalosi, Gerhild
AU - Hill, Adam T.
AU - Haworth, Charles S.
N1 - This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking iABC grant agreement n° 115721. The authors thank Mittal Makhija, Novartis Healthcare Pvt. Ltd, India, for providing medical writing and editorial support to draft the manuscript.Copyright © 2019. Published by Elsevier Ltd.
PY - 2019/10
Y1 - 2019/10
N2 - In patients with bronchiectasis (BE), infection with Pseudomonas aeruginosa (Pa) results in disease progression, frequent pulmonary exacerbations and lung function decline. However, at present, no inhaled antibiotics have been approved for the treatment of these patients. Tobramycin inhalation powder (TIP), approved for treatment of Pa infection in cystic fibrosis, could be a promising candidate. We aimed to assess effective and well-tolerated doses and regimens of TIP in BE patients with Pa infection. In this phase II, double-blind, placebo-controlled, randomised study, three different daily doses of TIP are administered either as continuous or cyclical regimens. The study protocol comprises 7–28 days of screening, 112 days of double-blind treatment and 56 days of follow-up. The plan was to enrol 180 patients (aged ≥18 years) with BE, documented Pa infection and a history of exacerbations. The primary outcome is change in sputum Pa density from baseline. Key secondary outcomes include number of pulmonary exacerbations, use of antipseudomonal antibiotics, serum and sputum tobramycin concentrations, quality of life and safety. Exploratory endpoints include lung clearance index, sputum inflammatory markers and microbiome analysis. As of October 2018, 107/180 patients were enrolled at 34 sites (six countries) following which recruitment was closed for administrative reasons unrelated to safety findings. Despite a reduced sample size from initially planned enrolment, the unique design may inform the benefit-risk profile of TIP in BE patients with chronic Pa infection. Moreover, several novel and exploratory endpoints (lung clearance index, inflammatory biomarkers, lung microbiome), will contribute to the advancement of research in this area.
AB - In patients with bronchiectasis (BE), infection with Pseudomonas aeruginosa (Pa) results in disease progression, frequent pulmonary exacerbations and lung function decline. However, at present, no inhaled antibiotics have been approved for the treatment of these patients. Tobramycin inhalation powder (TIP), approved for treatment of Pa infection in cystic fibrosis, could be a promising candidate. We aimed to assess effective and well-tolerated doses and regimens of TIP in BE patients with Pa infection. In this phase II, double-blind, placebo-controlled, randomised study, three different daily doses of TIP are administered either as continuous or cyclical regimens. The study protocol comprises 7–28 days of screening, 112 days of double-blind treatment and 56 days of follow-up. The plan was to enrol 180 patients (aged ≥18 years) with BE, documented Pa infection and a history of exacerbations. The primary outcome is change in sputum Pa density from baseline. Key secondary outcomes include number of pulmonary exacerbations, use of antipseudomonal antibiotics, serum and sputum tobramycin concentrations, quality of life and safety. Exploratory endpoints include lung clearance index, sputum inflammatory markers and microbiome analysis. As of October 2018, 107/180 patients were enrolled at 34 sites (six countries) following which recruitment was closed for administrative reasons unrelated to safety findings. Despite a reduced sample size from initially planned enrolment, the unique design may inform the benefit-risk profile of TIP in BE patients with chronic Pa infection. Moreover, several novel and exploratory endpoints (lung clearance index, inflammatory biomarkers, lung microbiome), will contribute to the advancement of research in this area.
KW - Bronchiectasis
KW - Dose and regimen
KW - Sputum Pa density
KW - Tobramycin inhalation powder
UR - http://www.scopus.com/inward/record.url?scp=85071340124&partnerID=8YFLogxK
U2 - 10.1016/j.pupt.2019.101834
DO - 10.1016/j.pupt.2019.101834
M3 - Article
C2 - 31433997
SN - 1094-5539
VL - 58
JO - Pulmonary Pharmacology & Therapeutics
JF - Pulmonary Pharmacology & Therapeutics
M1 - 101834
ER -