Back to Journals » International Journal of Chronic Obstructive Pulmonary Disease » Volume 13

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

Authors Fukushima Y, Nakatani Y, Ide Y, Sekino H, St Rose E, Siddiqui S, Maes A, Reisner C

Received 8 December 2017

Accepted for publication 12 March 2018

Published 13 April 2018 Volume 2018:13 Pages 1187—1194

DOI https://doi.org/10.2147/COPD.S159246

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
 

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]