Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler in Chinese Patients with COPD: A Subgroup Analysis of KRONOS

Chen Wang, Ting Yang, Jian Kang, Rongchang Chen, Li Zhao, Huijie He, Pryseley N Assam, Rong Su, Eric Bourne, Shaila Ballal, Kiernan DeAngelis, Paul Dorinsky, Chen Wang, Ting Yang, Jian Kang, Rongchang Chen, Li Zhao, Huijie He, Pryseley N Assam, Rong Su, Eric Bourne, Shaila Ballal, Kiernan DeAngelis, Paul Dorinsky

Abstract

Introduction: This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods: Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over weeks 12-24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint.

Results: In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference - 4 mL; P = 0.8316). BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints. BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI. All treatments were well tolerated.

Conclusions: Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β2-agonist), as well as symptoms and exacerbations relative to dual therapies. Findings support BGF MDI use in Chinese patients with moderate to very severe COPD.

Clinical trial registration: ClinicalTrials.gov NCT02497001.

Keywords: Bronchodilator agents; China; Chronic obstructive; Disease exacerbation; Pulmonary disease; Pulmonary function tests.

Figures

Fig. 1
Fig. 1
a Primary lung function endpoint (change from baseline in morning pre-dose trough FEV1 over time) and b cumulative proportion of responders based on the change from baseline in morning pre-dose trough FEV1 over weeks 12–24 (efficacy estimand, China mITT population). Error bars represent standard error values. The proportion of responders represents the percentage of patients with a change from baseline in FEV1 meeting or exceeding the cutoff points shown in the x-axis. BFF budesonide/formoterol fumarate, BGF budesonide/glycopyrrolate/formoterol fumarate, BUD/FORM DPI budesonide/formoterol fumarate dry powder inhaler, FEV1 forced expiratory volume in 1 s, GFF glycopyrrolate/formoterol fumarate, MDI metered dose inhaler, mITT modified intent-to-treat
Fig. 2
Fig. 2
Kaplan–Meier plot for time to first moderate/severe COPD exacerbation (efficacy estimand, China mITT population). BFF budesonide/formoterol fumarate, BGF budesonide/glycopyrrolate/formoterol fumarate, BUD/FORM DPI budesonide/formoterol fumarate dry powder inhaler, COPD chronic obstructive pulmonary disease, GFF glycopyrrolate/formoterol fumarate, MDI metered dose inhaler, mITT modified intent-to-treat

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