Comparative efficacy and safety of glycopyrronium/formoterol fixed-dose combination versus glycopyrronium monotherapy in patients with moderate-to–severe COPD

Abstract

Background: The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 mg/formoterol fumarate 12 mg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 mg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated. Methods: This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India. COPD patients aged ≥40 to ≤65 years, current or ex-smokers with FEV 1 /FVC <0.70, using ICS, LAMA, or LABA for ≥1 month were included. Subjects were randomized (1:1) to GB/FF or GLY for 12 weeks. The primary efficacy endpoint was the change from baseline in peak FEV 1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (CTRI/2017/02/007814). Results: Between March 2017 and July 2018, 331 patients were enrolled and randomized into GB/FF FDC (165 patients) and GLY monotherapy (166 patients) groups. At week 12, the difference in change from baseline in the peak FEV 1 for GB/FF DPI versus GLY was 0.115 L (SE = 0.02; 95% CI = 0.061, 0.170; P < 0.0001). Trough FEV 1 increased significantly in the GB/FF group compared to the GLY group with a treatment difference of 0.078 L (SE = 0.02; 95% CI = 0.015, 0.14; P = 0.01). There were no significant differences in adverse events between the groups. Conclusion: FDC of GB/FF (12.5/12 mg twice daily) as a DPI provides superior bronchodilation and lung function improvement over GLY (50 mg once daily) monotherapy. It is safe and well tolerated in symptomatic COPD patients.

Comparing Glycopyrronium/Formoterol Combination Therapy With Monotherapy in Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD): A Narrative Review

“…Multiple clinical trials have investigated the efficacy and safety of GFF combination therapy in patients diagnosed with COPD [ 14 ]. These studies have consistently demonstrated that GFF is comparable to tiotropium/formoterol (TFF) in enhancing lung function and assessing health status [ 12 , 13 ].…”

“…Moreover, GFF and TFF have exhibited favorable safety profiles and tolerability among symptomatic COPD patients [ 12 , 13 ]. In a comparative study evaluating twice-daily glycopyrronium/formoterol (GF) versus once-daily glycopyrronium (G), GF emerged as more effective in enhancing lung function and alleviating symptoms in individuals diagnosed with moderate-to-severe COPD [ 14 ]. Another clinical trial compared the efficacy and safety of GFF with umeclidinium/vilanterol (UV) fixed-dose combination over 24 weeks, revealing that GFF was non-inferior to UV concerning lung function improvement and health status assessment [ 15 ].…”

“…Another clinical trial compared the efficacy and safety of GFF with umeclidinium/vilanterol (UV) fixed-dose combination over 24 weeks, revealing that GFF was non-inferior to UV concerning lung function improvement and health status assessment [ 15 ]. Furthermore, a study assessing the efficacy and safety of a fixed-dose combination comprising fluticasone/formoterol/glycopyrronium (FFG) for COPD treatment demonstrated its effectiveness in enhancing lung function and alleviating symptoms among patients diagnosed with moderate-to-severe COPD [ 14 ].…”

“…The comparative analysis between glycopyrronium/formoterol fixed-dose combination (GB/FF) and glycopyrronium monotherapy in patients diagnosed with moderate-to-severe COPD has consistently demonstrated that GB/FF surpasses glycopyrronium monotherapy in terms of enhancing lung function and alleviating symptoms [ 13 , 14 , 34 ]. Furthermore, studies have indicated that GFF is non-inferior to TFF regarding improvements in lung function and health status assessment, with both treatments proving safe and well-tolerated for individuals experiencing symptomatic COPD [ 13 , 34 ].…”

“…The safety comparison between GB/FF and glycopyrronium monotherapy in patients diagnosed with moderate-to-severe COPD indicated that both treatments were well-tolerated and deemed safe for use [ 14 ]. Most AEs reported were of mild or moderate intensity, with low incidences observed in both treatment groups [ 14 ].…”