TY - JOUR T1 - The short term bronchodilator effects of the dual PDE3 and PDE4 inhibitor RPL554 in COPD JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01074-2018 SP - 1801074 AU - Dave Singh AU - Katharine Abbott-Banner AU - Thomas Bengtsson AU - Kenneth Newman Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/08/23/13993003.01074-2018.abstract N2 - Introduction: We investigated the short term bronchodilator effects of RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined with other bronchodilators in COPD patients with reversibility (>150 mL to short acting bronchodilators).Methods: Study 1: six way placebo controlled crossover study (n=36) with single doses of RPL554 (6 mg), salbutamol (200 µg), ipratropium (40 µg), RPL554+salbutamol, RPL554+ipratropium and placebo. Study 2: three way crossover study (n=30) of tiotropium (18 µg) combined with RPL554 (1.5 mg or 6 mg) or placebo for 3 days. FEV1, lung volumes and sGaw were measured.Results: Study 1; Peak FEV1 change compared to placebo was similar with RPL554, ipratropium and salbutamol (means 223, 199 and 187 mL respectively). The peak FEV1 was higher for RPL554+ipratropium versus ipratropium (mean difference 94 mL, p<0.0001) and RPL554+salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). Study 2 (day 3); both RPL554 doses caused greater peak FEV1 effects than placebo. The average FEV1 (0–12h) increase was greater with RPL554 6 mg only versus placebo (mean difference 65 mL p=0.0009). In both studies, lung volumes and sGaw showed greater RPL554 combination treatment effects versus monotherapy.Conclusion: RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Singh reports personal fees from Verona, during the conduct of the study; personal fees from Apellis, grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingleheim, grants and personal fees from Chiesi, personal fees from Cipla, personal fees from Genentech, grants and personal fees from GlaxoSmithKline, grants and personal fees from Glenmark, grants and personal fees from Menarini, grants and personal fees from Merck, grants and personal fees from Mundipharma, grants and personal fees from Novartis, personal fees from Peptinnovate, grants and personal fees from Pfizer, grants and personal fees from Pulmatrix, personal fees from Skyepharma, grants and personal fees from Teva, grants and personal fees from Therevance, grants and personal fees from Verona, outside the submitted work.Conflict of interest: Dr. Abbott-Banner has nothing to disclose.Conflict of interest: Mr. Bengtsson reports personal fees from Verona Pharma pls, during the conduct of the study; personal fees from Verona Pharma pls, outside the submitted work.Conflict of interest: Dr. Newman reports being a previous employee of Verona Pharma. ER -