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

BACKGROUND: Batefenterol is a novel bifunctional muscarinic antagonist β(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 FEV(1) ≥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 FEV(1) over 0–6 hours post-dose and trough FEV(1), 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 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.