<p>Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD</p>

Abstract

Background: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting β 2-agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4. Methods: In this randomized, double-blind, placebo-controlled, parallel-group Phase III study (NCT02343458), patients received GFF MDI 18/9.6 µg, glycopyrrolate (GP) MDI 18 µg, formoterol fumarate (FF) MDI 9.6 µg, or placebo MDI (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study. Results: Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all P≤0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group. Conclusion: GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China.

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

“…In summary, the FDC of GB/FF (12.5/12 mg) as a DPI in adult subjects with COPD was found to be safe and well tolerated. The safety profile of GB/FF DPI and GLY monotherapy in Indian patients was comparable to global[ 25 ] and Asian populations[ 28 ] and other licensed LAMA/LABA FDCs. [ 24 ]…”

“…[ 24 ] Further, the findings from this study are in line with the exploratory analysis of the Asian subpopulation of the PINNACLE 4 study. [ 28 ] Previous studies of GB/FF MDI in moderate-to–severe COPD patients from the global population[ 23 25 26 ] and Asian population[ 28 ] have shown improvements in daily, daytime, and nighttime symptom scores compared to monocomponents. Similarly, in the current study, improvement in these symptom scores seems to favor GB/FF DPI compared to GLY monotherapy at week 12.…”

The role of long-acting muscarinic antagonist/long-acting β agonist fixed-dose combination treatment for chronic obstructive pulmonary disease in China: a narrative review

“…To date, LAMA/LABA FDCs have been found to have feasible overall safety and tolerability profiles in studies including Chinese patients (duration of at least 24 weeks, up to 52 weeks). The rates of adverse events needing emergency treatment across treatment groups (GFF vs. GLY and FF) were similar or slightly higher in the placebo MDI group (46). Compared with TIO or OLO J Thorac Dis 2021 | https://dx.doi.org/10.21037/jtd-21-961 Guidelines have been issued by other organizations in more recent years, in which detailed statements describing the benefits of LAMA/LABA combination therapy and the recommended populations have been included.…”

“…A range of lung function measures show improvements with LAMA/LABA FDCs compared with placebo, monotherapy and the combination of salmeterol and fluticasone (SFC) (43)(44)(45)(46)(47). Chen et al (46) found that the trough FEV 1 was significantly better in patients receiving GFF than glycopyrronium (GP), formoterol (FF), and placebo (leastsquares mean differences: 98, 104, and 173 mL, respectively (all P≤0.0001). Zhong et al (43) found that GLY/IND was superior to SFC regarding the improvement in the trough FEV 1 .…”

“…Compared with SFC, GLY/IND significantly reduced the moderate or severe exacerbation rate by 31% (P=0.048). Chen et al (46) reported that in the Chinese subpopulation in the PINNACLE-4 study, the moderate or severe COPD exacerbation risk in the GFF treatment group was numerically lower than those in the GP, FF, and placebo groups; GFF reduced the risk of clinically important deterioration compared to monotherapies and the placebo.…”