The IMPACT Study – Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI And UMEC/VI In Patients With COPD: Efficacy And Safety In A Japanese Population

Abstract

Purpose

The Informing the Pathway of COPD Treatment (IMPACT) study demonstrated that single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduces moderate/severe exacerbation rates and improves lung function and health status versus FF/VI or UMEC/VI dual therapy in patients with symptomatic COPD and a history of exacerbations. This analysis evaluated the efficacy and safety of FF/UMEC/VI in patients enrolled in Japan.

Patients and methods

IMPACT was a 52-week, randomized, double-blind, multicenter study comparing FF/UMEC/VI 100/62.5/25 µg with FF/VI 100/25 µg or UMEC/VI 62.5/25 µg in patients ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the previous year. Endpoints included annual rate of on-treatment moderate/severe exacerbations (primary endpoint), time-to-first on-treatment moderate/severe exacerbation and change from baseline at Week 52 in trough FEV₁, post-bronchodilator FEV₁, St. George’s Respiratory Questionnaire, and COPD Assessment Test score. Safety was also assessed.

Results

The Japan subgroup accounted for only 4% (378/10,355) of the overall IMPACT intent-to-treat (ITT) population. In the Japan subgroup, FF/UMEC/VI reduced the annual rate of on-treatment moderate/severe exacerbations by 15% (95% CI: −20, 40) versus FF/VI (compared with 15% [10, 20] in the ITT) and 36% (95% CI: 6, 57) versus UMEC/VI (compared with 25% [19, 30] in the ITT). FF/UMEC/VI reduced moderate/severe exacerbation risk (time-to-first), improved lung function and health status at Week 52 versus both dual therapies. These results were in the same direction and of a generally similar magnitude to those seen in the overall ITT population. No new safety signals were identified in the Japan subgroup compared with the ITT population. Pneumonia incidence was higher with FF/UMEC/VI and FF/VI versus UMEC/VI.

Conclusion

These results highlight the favorable benefit–risk profile of FF/UMEC/VI single-inhaler triple therapy compared with FF/VI or UMEC/VI dual therapy in patients in Japan with symptomatic COPD and ≥1 exacerbation in the prior year.

Keywords:

• triple therapy
• fluticasone furoate
• Japan
• umeclidinium
• vilanterol
• COPD exacerbation

Acknowledgments

Editorial support (in the form of writing assistance, assembling figures, collating author comments, grammatical editing, and referencing) was provided by Chrystelle Rasamison and Hayley Mukherjee, PhD, at Fishawack Indicia Ltd, UK, and was funded by GSK. We thank the patients, families, and investigators in Japan who participated in the IMPACT trial. These data were presented in part at the 59th Annual Meeting of the Japanese Respiratory Society, Tokyo, Japan, 12 April 2019.

Ethics Approval And Informed Consent

The study was conducted in accordance with Good Clinical Practice (GCP) guidelines and the provisions of the Declaration of Helsinki. All patients enrolled in IMPACT provided written informed consent. The study protocol, any amendments, the informed consent, and other information that required preapproval were reviewed and approved by national, regional, or investigational site ethics committees or institutional review boards, in accordance with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use GCP and applicable for country-specific requirements, including US 21 Code of Federal Regulations 312.3(b) for constitution of independent ethics committees.

Abbreviations

AE, adverse event; AESI, adverse event of special interest; BFF, budesonide/formoterol fumarate; BGF, budesonide/glycopyrrolate/formoterol fumarate; BMI, body mass index; CAT, COPD Assessment Test; FF, fluticasone furoate; GFF, glycopyrrolate/formoterol fumarate; HRQoL, health-related quality of life; ICS, inhaled corticosteroid; IMPACT, InforMing the PAthway of COPD Treatment; ITT, intent-to-treat; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MACE, major adverse cardiovascular events; RTI, respiratory tract infection; SAE, serious adverse event; SGRQ, St. George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Data Availability

Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.

Author contributions

All authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors, take responsibility for the integrity of the work as a whole, contributed to the writing and reviewing of the manuscript, and have given final approval for the version to be published. All authors had full access to the data in this study, take complete responsibility for the integrity of the data and accuracy of the data analysis and agree to be accountable for all aspects of the work. M Kato and K Tomii contributed to the acquisition of data, K Hashimoto, Y Nezu, T Ishii, CE Jones, S Kilbride, A Gross, and C Clifton contributed to the data analysis and interpretation, DA Lipson contributed to the conception and design of the study, and to the data analysis and interpretation.

Disclosure

Motokazu Kato has received lecture honoraria from GSK, AstraZeneca, Nippon Boehringer Ingelheim, and Novartis Pharma. Keisuke Tomii has received lecture honoraria from Nippon Boehringer Ingelheim, AstraZeneca, GSK, Novartis Pharma, and Teijin Pharma. Kenichi Hashimoto, Takeo Ishii, C. Elaine Jones, Sally Kilbride, Annette S. Gross, Christine S. Clifton, and David A. Lipson are GSK employees and hold stock/shares in GSK. Yasuko Nezu is an employee of GSK. Ellipta is owned by or licensed to the GSK Group of Companies. The authors report no other conflicts of interest in this work.