Comparison of a dry powder inhaler (DPI) to a pressurized metered-dose inhaler (pMDI) formulation of extra fine beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) in patients with COPD: The TRI-D study

Abstract

Introduction: A DPI formulation (NEXThaler®) of the extra fine BDP/FF/GB triple therapy has been developed as an alternative to pMDI to meet patients’ preference and to provide treatment options. Aims and Objectives: To demonstrate the non-inferiority of the DPI versus pMDI formulations of extra fine BDP/FF/GB on lung function. Methods: TRI-D was a, randomized, double-blind, double-dummy, active controlled, 3-way cross-over trial comparing 4 weeks of treatment with BDP/FF/GB 100/6/12.5 µg DPI and pMDI and BDP/FF 100/6 µg pMDI each delivered as 2 inhalations bid, separated by 2-week wash-outs in patients with stable, moderate-to-severe COPD. The co-primary efficacy endpoints were the change from baseline in FEV1 AUC0-12h normalised by time and in trough FEV1 at 24 hours on Day 28. Treatment-emergent adverse events (TEAEs) were collected. Results: 366 patients were randomized. Non-inferiority of BDP/FF/GB DPI vs pMDI was demonstrated for both co‑primary endpoints, with the lower limits of confidence interval of the adjusted mean differences falling above the non-inferiority threshold of -50 mL (-35 mL and -15 mL). Both DPI and pMDI triple therapies significantly improved FEV1 AUC0‑12h vs BDP/FF pMDI by 85 and 105 mL, respectively (p Conclusion: DPI and pMDI formulations of extra fine BDP/FF/GB demonstrated similar efficacy and safety in patients with COPD supporting the new DPI formulation as a valid option for both patient and physician.