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

Abstract

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.

Journal

Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis

Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis

Journal ID (publisher-id): International Journal of COPD

Title: International Journal of Chronic Obstructive Pulmonary Disease

Publisher: Dove Medical Press

ISSN (Print): 1176-9106

ISSN (Electronic): 1178-2005

Publication date Collection: 2018

Publication date (Electronic): 13 April 2018

Volume: 13

Pages: 1187-1194

Affiliations

[1 ]Department of Internal Medicine, Fukuwa Clinic, Tokyo, Japan

[2 ]Department of Internal Medicine, Nakatani Hospital, Hyogo, Japan

[3 ]Department of Internal Medicine, Tokyo Center Clinic, Tokyo, Japan

[4 ]Department of Internal Medicine, Sekino Hospital, Tokyo, Japan

[5 ]Pearl – a member of the AstraZeneca Group, Morristown, NJ, USA

[6 ]AstraZeneca, Gaithersburg, MD, USA

Author notes

Correspondence: Colin Reisner, Pearl – a member of the AstraZeneca Group, 280 Headquarters Plaza, East Tower, Morristown, NJ 07960, USA, Email colin.reisner@ 123456astrazeneca.com

Article

Publisher ID: copd-13-1187

DOI: 10.2147/COPD.S159246

PMC ID: 5905841

Copyright statement: © 2018 Fukushima et al. This work is published and licensed by Dove Medical Press Limited

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Categories

Subject: Original Research