2. Academic Validation
  3. Randomized dose-finding study of batefenterol via dry powder inhaler in patients with COPD

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

  • Int J Chron Obstruct Pulmon Dis. 2019 Mar 8:14:615-629. doi: 10.2147/COPD.S190603.
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-Santamaria 10
Affiliations

Affiliations

  • 1 GSK, Research and Development, Research Triangle Park, NC, USA, courtney.c.crim@gsk.com.
  • 2 Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • 3 S. Carolina Pharmaceutical Research, Spartanburg, SC, USA.
  • 4 Klinische Forschung Berlin GbR, Berlin, Germany.
  • 5 Clinical Trials Division, Crisor LLC, Clinical Research Institute, Medford OR, USA.
  • 6 GSK, Global Medical, Stockley Park, Uxbridge, Middlesex, UK.
  • 7 Upstate Pharmaceutical Research, Greenville, SC, USA.
  • 8 PAREXEL International, Durham, NC, USA.
  • 9 GSK, Clinical Statistics, Stockley Park, Uxbridge, Middlesex, UK.
  • 10 GSK, Research and Development, Collegeville, PA, USA.
PMID: 30880951 DOI: 10.2147/COPD.S190603
Abstract

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; dose-response; dual-pharmacophore; muscarinic antagonist β2-agonist.

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