Randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of three doses of co-suspension delivery technology glycopyrronium MDI in Japanese patients with moderate-to-severe COPD

PURPOSE: Due to the burden of COPD in Japan, new pharmacologic treatments are needed to meet patient requirements. This study assessed the efficacy and safety of glycopyrronium (GP) delivered via metered dose inhaler (MDI) in Japanese patients with moderate-to-severe COPD. METHODS: This Phase IIb, multicenter, randomized, double-blind, 7-day, crossover study compared GP MDI 28.8, 14.4, and 7.2 μg with placebo MDI (all administered as two inhalations, twice daily). The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV(1)) on Day 8. Secondary endpoints included FEV(1) area under the curve from 0 to 2 hours (AUC(0–2)) and peak change from baseline in FEV(1) on Days 1 and 8 and forced vital capacity AUC(0–2) on Day 8. Safety was also assessed. ClinicalTrials.gov Identifier: NCT03256552; http://www.ClinicalTrials.gov. RESULTS: Sixty-six patients were randomized and 62 were included in the modified intent-to-treat population (mean age 67.5 years). All three GP MDI doses significantly improved change from baseline in morning pre-dose trough FEV(1) on Day 8 compared with placebo MDI (least squares mean differences 108–131 mL; all p<0.0001). Significant improvements in secondary efficacy endpoints were also observed for all three GP MDI doses compared with placebo MDI (all p<0.0001). Dose–response plateaued at GP MDI 14.4 μg. No significant safety findings were observed with any GP MDI dose or placebo MDI. CONCLUSIONS: The results of this study suggest that GP MDI 14.4 μg (7.2 μg per inhalation) is the most appropriate dose for use in Phase III studies in Japanese patients with moderate-to-severe COPD.