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Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies

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Abstract

Purpose

To compare the efficacy and safety of two long-acting dual bronchodilator combinations: indacaterol/glycopyrrolate (IND/GLY) versus umeclidinium/vilanterol (UMEC/VI).

Methods

Studies A2349 and A2350 were replicate, randomized, double-blind, double-dummy, active-controlled, cross-over studies in patients with moderate-to-severe COPD. Patients were randomized to sequential 12-week treatments of twice-daily IND/GLY 27.5/15.6 μg and once-daily UMEC/VI 62.5/25 μg, each separated by a 3-week washout. The primary objective was to demonstrate non-inferiority of IND/GLY compared with UMEC/VI in terms of the 24-h forced expiratory volume in 1 s profile at week 12 (FEV1 AUC0–24). Rescue medication use, symptom control, and safety were assessed throughout.

Results

Both treatments delivered substantial bronchodilation over 12 weeks, with improvements in FEV1 AUC0–24h at week 12 of 232 and 185 mL for IND/GLY, and 244 and 203 mL with UMEC/VI in Studies A2349 and A2350, respectively. The primary efficacy objective of non-inferiority of IND/GLY relative to UMEC/VI was not met as the lower bound of the confidence interval for the LS treatment comparison was below the pre-specified non-inferiority margin of −20 mL in both studies: −26.9 and −34.2 mL, respectively (LS mean between-treatment differences: −11.5 and −18.2 mL). Both drugs were well tolerated, with AE profiles consistent with their respective prescribing information.

Conclusions

IND/GLY and UMEC/VI provided clinically meaningful and comparable bronchodilation. Non-inferiority of IND/GLY to UMEC/VI could not be declared although between-treatment differences were not clinically relevant. The data support the use of IND/GLY as an efficacious and well tolerated treatment option in patients with COPD. (ClinicalTrials.gov NCT02487446 and NCT02487498)

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Acknowledgements

The authors take full responsibility for the scope, direction, content, and editorial decisions relating to the manuscript, and were involved at all stages of development and approved the submitted manuscript. The authors received no compensation related to the development of the manuscript. This analysis was sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States. Medical writing assistance was provided by Colette O’Sullivan, PhD, of Scriva Medical Communications Ltd, a professional medical writer funded by Novartis.

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Authors and Affiliations

Authors

Contributions

TA and DB contributed to the conception and the design of the study. EK, GTF, SS, TG, AY, RF, SM, BS, TA, and DB contributed to the acquisition and analysis of the data and take full responsibility for the scope, direction, content, and editorial decisions relating to the manuscript. All authors were involved at all stages of development and approved the submitted manuscript. The authors received no compensation related to the development of the manuscript.

Corresponding author

Correspondence to Donald Banerji.

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Conflict of interest

EK and GTF were principal investigators on the studies. SS and TG are employees of Sunovion Pharmaceuticals Inc. AY, RF, SM, BS, TA, and DB are employees of Novartis Pharmaceuticals Corporation or Novartis Healthcare Pvt. Ltd.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (ClinicalTrials.gov NCT02487446 and NCT02487498).

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Kerwin, E., Ferguson, G.T., Sanjar, S. et al. Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies. Lung 195, 739–747 (2017). https://doi.org/10.1007/s00408-017-0055-9

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  • DOI: https://doi.org/10.1007/s00408-017-0055-9

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