Efficacy and safety of glycopyrronium/formoterol delivered via a dry powder inhaler in patients with moderate to severe chronic obstructive pulmonary disease

Abstract

Background: We designed this randomised, open-label, parallel group, multi-centre study to investigate the efficacy and safety of glycopyrronium/formoterol, a long-acting muscarinic antagonist/long-acting β2-agonist fixed dose combination, delivered through a dry powder inhaler (DPI) in patients with chronic obstructive pulmonary disease (COPD). Material and Methods: We randomised (1:1) patients with moderate to severe COPD (N = 356) to receive glycopyrronium 25 µg/formoterol 12 µg via DPI twice daily (GF-DPI) or glycopyrronium 50 µg monotherapy via DPI once daily (G-DPI). The primary study endpoint was the mean change from the baseline in pre-dose trough-forced expiratory volume in one second (FEV 1 ) at 12 weeks. Results: At week 12, the mean increase from the baseline in pre-dose trough FEV 1 was higher in the GF-DPI group (120 ml) than in the G-DPI (60 ml) group. The mean difference (MD) between treatment groups was 0.06 L (95% CI: 0.00–0.12 L, P < 0.0001 for non-inferiority). At week 12, the mean pre-dose forced vital capacity (FVC), 1 hour post-dose FEV 1 , and post-dose FVC increased significantly from the baseline only in the GF-DPI group (p < 0.0001). The reduction in the COPD assessment test score was greater in the GF-DPI group (p = 0.0379). The average daily number of puffs of rescue medication and the reduction in mean modified Medical Research Council scale, COPD, and Asthma Sleep Impact Scale score at week 12 were similar between groups (p > 0.05). Overall, 35 adverse events and two serious adverse events unrelated to study drugs were reported. Both groups had similar results for overall drug safety. Conclusion: The results demonstrate efficacy and safety of GF-DPI in Indian patients with moderate to severe COPD. Treatment with GF-DPI significantly improved the lung function and quality of life and was well tolerated.

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 ].…”

“…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 ].…”

“…The frequency of adverse events may vary depending on the study design and patient population. In a study comparing GFF combination therapy with glycopyrronium monotherapy, the most common AEs reported in the GFF group were headache (1.12%) and abnormal blood pressure (8.43%) [ 12 ]. Similarly, common AEs in another study included dry mouth, nasopharyngitis, cough, bacterial URTI, and headache [ 26 ].…”

“…Extensive research has thoroughly examined the respiratory safety profile of GFF combination therapy in individuals diagnosed with COPD. Findings from these studies suggest that GFF treatment significantly enhances lung function and quality of life while maintaining high patient tolerability [ 12 , 18 ]. Moreover, evidence indicates that GFF is safe and effective, with no discernible increase in safety risks compared to monotherapy or placebo.…”

“…While glycopyrronium's anticholinergic properties target specific receptors implicated in bronchoconstriction and secretions, formoterol's beta-2 agonist activity enhances bronchodilation by fostering cyclic AMP production. This collaborative therapy provides an effective strategy for treating moderate-to-severe COPD by concurrently addressing bronchoconstriction and airway inflammation [11][12][13].…”