Peak Inspiratory Flow Rate in COPD: An Analysis of Clinical Trial and Real-World Data

Martin Anderson; Kathryn Collison; M Bradley Drummond; Melanie Hamilton; Renu Jain; Neil Martin; Richard A Mularski; Mike Thomas; Chang-Qing Zhu; Gary T Ferguson

doi:10.2147/COPD.S291554

Peak Inspiratory Flow Rate in COPD: An Analysis of Clinical Trial and Real-World Data

Int J Chron Obstruct Pulmon Dis. 2021 Apr 12:16:933-943. doi: 10.2147/COPD.S291554. eCollection 2021.

Authors

Affiliations

¹ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
² Respiratory Therapy Area, GSK, Research Triangle Park, NC, USA.
³ Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ R&D, GSK, Ware, Hertfordshire, UK.
⁵ Global Medical Affairs, GSK, Brentford, Middlesex, UK.
⁶ Institute for Lung Health, University of Leicester, Leicester, Leicestershire, UK.
⁷ Department of Pulmonary and Critical Care Medicine, Kaiser Permanente Northwest Center for Health Research, Portland, OR, USA.
⁸ Primary Care Research, University of Southampton, Southampton, UK.
⁹ Biostatistics, GSK, Stockley Park West, Uxbridge, Middlesex, UK.
¹⁰ Pulmonary Research, Institute of Southeast Michigan, Farmington Hills, MI, USA.

Abstract

Background: The influence of peak inspiratory flow (PIF) on dose delivery from dry powder inhalers (DPIs) and association with treatment efficacy in patients with chronic obstructive pulmonary disease (COPD) has not been fully determined. In vitro studies have demonstrated adequate dose delivery through ELLIPTA DPI at PIF ≥30 L/min. This analysis of two clinical trials and a real-world population of COPD patients determined spirometric PIF distribution, and explored the relationship between PIF and outcomes in the trials.

Methods: The replicate Phase IV, 12-week, randomized, double-blind 207608/207609 (NCT03478683/NCT03478696) trials evaluated fluticasone furoate/umeclidinium/vilanterol via ELLIPTA DPI versus budesonide/formoterol+tiotropium in COPD patients. This post hoc analysis assessed spirometric PIF distribution at screening and relationship between PIF and lung function outcomes in the pooled 207608/207609 population. Spirometric PIF distributions in a real-world population of COPD patients were evaluated by retrospective analysis of the Kaiser Permanente Northwest (KPNW) database to assess similarities between clinical trial and real-world populations.

Results: A total of 1460 (207608/207609) and 3282 (KPNW) patients were included. There was considerable overlap between spirometric PIF distributions for both populations. Overall, 99.7% and 99.8% of the 207608/207609 and KPNW populations, respectively, reported spirometric PIF ≥50 L/min, estimated as equivalent to ELLIPTA PIFR ≥30 L/min. In the 207608/207609 combined analysis, there was no significant interaction between spirometric PIF and treatment for lung function endpoints, indicating treatment effect is independent of PIF.

Conclusion: Nearly all COPD patients in the 207608/207609 and KPNW populations achieved spirometric PIF values estimated as equivalent to PIFR of ≥30 L/min through the ELLIPTA DPI. Lack of correlation between spirometric PIF at screening and treatment efficacy aligns with consistent dose performance from the ELLIPTA DPI across a wide range of PIFs, achieved by patients with COPD of all severities.

Keywords: COPD; DPI; inhaled triple therapy; patient outcomes; peak inspiratory flow rate; real-world studies.

Publication types

Randomized Controlled Trial

MeSH terms

Administration, Inhalation
Bronchodilator Agents / adverse effects
Dry Powder Inhalers
Humans
Pulmonary Disease, Chronic Obstructive* / diagnosis
Pulmonary Disease, Chronic Obstructive* / drug therapy
Retrospective Studies
Spirometry

Substances

Bronchodilator Agents

Grants and funding

These studies were funded by GSK (study number 207608; NCT03478683; study number 207609; NCT03478696). The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. ELLIPTA and Diskus are owned by or licensed to the GSK Group of Companies. HandiHaler is a trademark of Boehringer Ingelheim International GmbH.