Randomized Dose-Finding Study Of Batefenterol Via Dry Powder Inhaler In Patients With Copd

Background: Batefenterol is a novel bifunctional muscarinic antagonist beta(2)-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 mu g, placebo, or umeclidinium/vilanterol (UMEC/VI) 62.5/25 mu g 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 E-max 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 mu g were comparable with those with UMEC/VI. Batefenterol was well tolerated and no new safety signals were observed.Conclusion: Batefenterol 300 mu g may represent the optimal dose for Phase III studies.