Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection

Design of a dose-finding study (iBEST-1)

iBEST-1 Trial Team

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number101834
JournalPulmonary Pharmacology and Therapeutics
Volume58
DOIs
Publication statusPublished - Oct 1 2019

Fingerprint

Tobramycin
Bronchiectasis
Powders
Pseudomonas aeruginosa
Inhalation
Pseudomonas Infections
Safety
Lung
Infection
Sputum
Microbiota
Anti-Bacterial Agents
Biomarkers
Screening
Cystic Fibrosis
Sample Size
Disease Progression
Therapeutics
Placebos
Quality of Life

Keywords

  • Bronchiectasis
  • Dose and regimen
  • Sputum Pa density
  • Tobramycin inhalation powder

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

@article{ee78417c36634b6e89addd4b406eba2e,
title = "Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection: Design of a dose-finding study (iBEST-1)",
abstract = "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.",
keywords = "Bronchiectasis, Dose and regimen, Sputum Pa density, Tobramycin inhalation powder",
author = "{iBEST-1 Trial Team} and Loebinger, {Michael R.} and Eva Polverino and Francesco Blasi and Elborn, {Stuart J.} and Chalmers, {James D.} and Tiddens, {Harm AWM} and Herman Goossens and Michael Tunney and Wenchun Zhou and Gerhild Angyalosi and Hill, {Adam T.} and Haworth, {Charles S.}",
year = "2019",
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doi = "10.1016/j.pupt.2019.101834",
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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 - iBEST-1 Trial Team

AU - Loebinger, Michael R.

AU - Polverino, Eva

AU - Blasi, Francesco

AU - Elborn, Stuart J.

AU - Chalmers, James D.

AU - Tiddens, Harm AWM

AU - Goossens, Herman

AU - Tunney, Michael

AU - Zhou, Wenchun

AU - Angyalosi, Gerhild

AU - Hill, Adam T.

AU - Haworth, Charles S.

PY - 2019/10/1

Y1 - 2019/10/1

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.

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KW - Dose and regimen

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