Randomized dose-finding study of batefenterol via dry powder inhaler in patients with COPD
Received 12 October 2018
Accepted for publication 23 January 2019
Published 8 March 2019 Volume 2019:14 Pages 615—629
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Courtney Crim,1 Michael L Watkins,1 Eric D Bateman,2 Gregory J Feldman,3 Isabelle Schenkenberger,4 Edward M Kerwin,5 Catriona Crawford,6 Krishna Pudi,7 Shuyen Ho,8 Charlotte Baidoo,9 Ramiro Castro-Santamaria10
1GSK, Research and Development, Research Triangle Park, NC, USA; 2Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa; 3S. Carolina Pharmaceutical Research, Spartanburg, SC, USA; 4Klinische Forschung Berlin GbR, Berlin, Germany; 5Clinical Trials Division, Crisor LLC, Clinical Research Institute, Medford OR, USA; 6GSK, Global Medical, Stockley Park, Uxbridge, Middlesex, UK; 7Upstate Pharmaceutical Research, Greenville, SC, USA; 8PAREXEL International, Durham, NC, USA; 9GSK, Clinical Statistics, Stockley Park, Uxbridge, Middlesex, UK; 10GSK, Research and Development, Collegeville, PA, USA
Background: Batefenterol is a novel bifunctional muscarinic antagonist β2-agonist in development for COPD. The primary objective of this randomized, double-blind, placebo-controlled, active comparator, Phase IIb study was to model the dose–response of batefenterol and select a dose for Phase III development.
Patients and methods: Patients aged ≥40 years with COPD and FEV1 ≥30% and ≤70% predicted normal were randomized equally to batefenterol 37.5, 75, 150, 300, or 600 µg, placebo, or umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg once daily. The primary and secondary endpoints were weighted-mean FEV1 over 0–6 hours post-dose and trough FEV1, analyzed by Bayesian and maximum likelihood estimation Emax of dose–response modeling, respectively, on day 42.
Results: In the intent-to-treat population (N=323), all batefenterol doses demonstrated statistically and clinically significant improvements from baseline vs placebo in the primary and secondary endpoints (191.1–292.8 and 182.2–244.8 mL, respectively), with a relatively flat dose–response. In the subgroup reversible to salbutamol, there were greater differences between batefenterol doses. Lung function improvements with batefenterol ≥150 µg were comparable with those with UMEC/VI. Batefenterol was well tolerated and no new safety signals were observed.
Conclusion: Batefenterol 300 µg may represent the optimal dose for Phase III studies.
Keywords: bifunctional, bronchodilator, dual-pharmacophore, dose–response, muscarinic antagonist β2-agonist
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]