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
Received 8 December 2017
Accepted for publication 12 March 2018
Published 13 April 2018 Volume 2018:13 Pages 1187—1194
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Charles Downs
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Yasushi Fukushima,1 Yuji Nakatani,2 Yumiko Ide,3 Hisakuni Sekino,4 Earl St Rose,5 Shahid Siddiqui,6 Andrea Maes,5 Colin Reisner5,6
1Department of Internal Medicine, Fukuwa Clinic, Tokyo, Japan; 2Department of Internal Medicine, Nakatani Hospital, Hyogo, Japan; 3Department of Internal Medicine, Tokyo Center Clinic, Tokyo, Japan; 4Department of Internal Medicine, Sekino Hospital, Tokyo, Japan; 5Pearl – a member of the AstraZeneca Group, Morristown, NJ, USA; 6AstraZeneca, Gaithersburg, MD, USA
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 (FEV1) on Day 8. Secondary endpoints included FEV1 area under the curve from 0 to 2 hours (AUC0–2) and peak change from baseline in FEV1 on Days 1 and 8 and forced vital capacity AUC0–2 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 FEV1 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.
Keywords: bronchodilator agents, dose–response relationship, forced expiratory volume, metered dose inhalers, COPD
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