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

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.