Background: The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5 μg glycopyrronium (GB)/12 μg formoterol fumarate (FF)/250 μg fluticasone propionate (FP), compared to 50 μg GB co-administered with a fixed dose of 12 μg FF/250 μg FP in subjects with COPD.
Methods: This was a 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 forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70, using mono/dual therapy with inhaled corticosteroids (ICSs), long-acting muscarinic antagonists (LAMAs), or long-acting β-agonists (LABAs) for ≥1 month, were included. Subjects were randomised 1:1 to GB/FF/FP or GB+FF/FP for 12 weeks. The primary efficacy end-point 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 (identifier number: CTRI/2019/01/017156).
Results: Between 23 March 2019 and 14 February 2020, 396 subjects were enrolled, with 198 patients each in the fixed-triple (GB/FF/FP) and open-triple (GB+FF/FP) groups. The difference in least-square mean (LSM) changes in pre-dose FEV1 from baseline at 12 weeks was noninferior between the groups (p<0.05). The LSM change from baseline in post-dose FEV1 was comparable (p=0.38). A 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.
Conclusions: Fixed triple therapy with GB/FF/FP provides comparable bronchodilation and lung function improvement as open-triple therapy. It is safe and well tolerated in symptomatic COPD patients with a history of exacerbations.
Copyright ©The authors 2021.