Randomized dose-finding study of batefenterol via dry powder inhaler in patients with COPD

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 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 E_max of dose-response modeling, respectively, on day 42.

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.

Batefenterol 300 µg may represent the optimal dose for Phase III studies.