+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD: A Subgroup Analysis of the KRONOS Study

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          KRONOS, a Phase III, multicenter, randomized, double-blind study (NCT02497001) conducted in Canada, China, Japan, and the USA, assessed the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), a triple fixed-dose combination therapy, relative to dual therapies in patients with moderate-to-very severe COPD. Here we present findings from the Japanese subgroup of KRONOS.


          Patients received BGF MDI 320/18/9.6μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12μg twice-daily for 24 weeks. The primary endpoint was the change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV 1) over Weeks 12–24. Symptoms, quality of life, exacerbations, and safety were also assessed.


          In total, 416 Japanese patients (21.9% of the global KRONOS population) were randomized and treated with BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Nominally significant improvements in the change from baseline in morning pre-dose trough FEV 1 over Weeks 12–24 were observed for BGF MDI vs GFF MDI (least squares mean [LSM] difference 37 mL, 95% confidence interval [CI] 3, 72; P=0.0337) and BFF MDI (67 mL; 95% CI 25, 109; P=0.0020). Treatment with BGF MDI led to a nominally significant reduction in the rate of moderate/severe exacerbations vs GFF MDI (rate ratio 0.40, 95% CI 0.19, 0.83; P=0.0142). Compared with dual therapies, numerical improvements were observed with BGF MDI for Transition Dyspnea Index focal score and the change from baseline in Evaluating Respiratory Symptoms in COPD total score ( P≤0.3899). All treatments were generally well tolerated.


          BGF MDI nominally significantly improved lung function and numerically improved symptoms vs GFF MDI and BFF MDI. BGF MDI nominally significantly reduced exacerbations vs GFF MDI in Japanese patients with COPD. Efficacy and safety findings were generally comparable to those in the global KRONOS population.

          Related collections

          Most cited references 16

          • Record: found
          • Abstract: found
          • Article: not found

          Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

          This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer-reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations.
            • Record: found
            • Abstract: found
            • Article: not found

            The natural history of community-acquired pneumonia in COPD patients: a population database analysis.

            Patients with Chronic Obstructive Pulmonary Disease (COPD) are at higher risk of developing Community-Acquired Pneumonia (CAP) than patients in the general population. However, no studies have been performed in general practice assessing longitudinal incidence rates for CAP in COPD patients or risk factors for pneumonia onset. A cohort of COPD patients aged ≥ 45 years, was identified in the General Research Practice Database (GPRD) between 1996 and 2005, and annual and 10-year incidence rates of CAP evaluated. A nested case-control analysis was performed, comparing descriptors in COPD patients with and without CAP using conditional logistic regression generating odds ratios (OR) and 95% confidence intervals (CI). The COPD cohort consisted of 40,414 adults. During the observation period, 3149 patients (8%) experienced CAP, producing an incidence rate of 22.4 (95% CI 21.7-23.2) per 1000 person years. 92% of patients with pneumonia diagnosis had suffered only one episode. Multivariate modelling of pneumonia descriptors in COPD indicate that age over 65 years was significantly associated with increased risk of CAP. Other independent risk factors associated with CAP were co-morbidities including congestive heart failure (OR 1.4, 95% CI 1.2-1.6), and dementia (OR 2.6, 95%CI 1.9-3.). Prior severe COPD exacerbations requiring hospitalization (OR 2.7, 95% CI 2.3-3.2) and severe COPD requiring home oxygen or nebulised therapy (OR 1.4, 95% CI 1.1-1.6) were also significantly associated with risk of CAP. COPD patients presenting in general practice with specific co-morbidities, severe COPD, and age >65 years are at increased risk of CAP. Copyright © 2012 Elsevier Ltd. All rights reserved.
              • Record: found
              • Abstract: not found
              • Article: not found

              Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial


                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                23 December 2019
                : 14
                : 2979-2991
                [1 ]Department of Respiratory Medicine, Tohoku University Graduate School of Medicine , Sendai, Japan
                [2 ]Department of Internal Medicine, Fukuwa Clinic , Tokyo, Japan
                [3 ]Clinical Research Center, National Hospital Organization, Kinki-Chuo Chest Medical Center , Osaka, Japan
                [4 ]Respiratory Center, Matsusaka Municipal Hospital , Matsusaka, Japan
                [5 ]Pulmonary Research Institute of Southeast Michigan , Farmington Hills, MI, USA
                [6 ]LungenClinic Grosshansdorf and Christian-Albrechts University Kiel, Airway Research Center North, Member of the German Center for Lung Research (DZL) , Grosshansdorf, Germany
                [7 ]AstraZeneca K.K ., Osaka, Japan
                [8 ]AstraZeneca , Durham, NC, USA
                [9 ]AstraZeneca , Morristown, NJ, USA
                [10 ]Formerly of AstraZeneca , Durham, NC, USA
                [11 ]AstraZeneca , Gothenburg, Sweden
                Author notes
                Correspondence: Masakazu Ichinose Department of Respiratory Medicine, Tohoku University Graduate School of Medicine , Sendai, JapanTel +81-22-717-8534 Email
                © 2019 Ichinose et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (

                Page count
                Figures: 2, Tables: 5, References: 26, Pages: 13
                Original Research


                Comment on this article