Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial

Abstract

BackgroundInvestigating the safety and efficacy of single-inhaler triple therapy with glycopyrronium (GB) 12.5 μg/formoterol fumarate (FF) 12 μg/fluticasone propionate (FP) 250 μg, compared to GB 50 μg co-administered with a fixed dose of FF 12 μg/FP 250 μg in subjects with COPD.MethodsA phase 3, randomised, double-blind, active-control, parallel-group, noninferiority study conducted at 20 sites across India. COPD patients aged ≥40 to ≤75 years, with FEV1/FVC <0.70, using mono/dual therapy with ICS, LAMA, or LABA for ≥1 month, were included. Subjects were randomised 1:1 to GB/FF/FP or GB+FF/FP for 12 weeks. Primary efficacy endpoint was the change from baseline in trough FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (CTRI Reg No: CTRI/2019/01/017156).ResultsBetween March 23, 2019 and February 14, 2020, 396 subjects were enrolled, 198 patients each in the fixed-triple (GB/FF/FP) and open-triple (GB+FF/FP) groups. The difference in LSM changes in predose FEV1 from baseline at 12 weeks was noninferior between the groups (p<0.05). The LSM change from baseline in postdose FEV1 was comparable (p=0.38). Superiority test showed comparable efficacy (p =0.12) for the difference in mean change from baseline in trough FEV1 between the groups. Adverse events (mild or moderate) were recorded in 25.3% and 24.9% of subjects in the GB/FF/FP and GB+FF/FP groups.ConclusionsFixed triple therapy with GB/FF/FP provides comparable bronchodilation and lung function improvement like open triple therapy. It is safe and well-tolerated in symptomatic COPD patients with a history of exacerbations.

ICS/Ultra LABA in the Treatment of Obstructive Airway Diseases: A Consensus of Indian Experts

“…However, for patients predisposed towards poor adherence, single-inhaler triple therapy could be considered. A recent study showed that bronchodilation and lung-function improvement was comparable in the single-inhaler triple therapy and open triple therapy [ 59 ]. Box 8 represents expert panel recommendations on the use of triple therapy in COPD.…”

Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus

“… 4 , 32 Two previous randomized trials showed comparable efficacy of SITT and MITT in reducing the risk of exacerbations. 33 , 34 A recent Delphi study by Lopez-Campos et al also noted the agreement on triple therapy resulting in improvement in lung function and reduction in exacerbation risk in patients with COPD. 35 A consensus was reached in the current Delphi study regarding triple therapy being more beneficial compared to dual therapy in frequent exacerbators and with SITT being considered more effective than MITT in reducing exacerbations.…”

Triple Therapy for COPD: Historical Perspective and Current Controversies

“…Finally, in addition to these triple combinations already on the market, there are at least two more in process of development. On the one hand, the combination of Fluticasone propionate with formoterol and glycopyrronium has recently been published after its first phase 3 trial in India 27 . It is administered in a pMDI every 12 hours and shows similar efficacy to open-label triple therapy.…”