TY - JOUR T1 - The novel bronchodilator navafenterol: a phase 2a, multi-centre, randomised, double-blind, placebo-controlled crossover trial in COPD JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00972-2021 SP - 2100972 AU - Dave Singh AU - Jutta Beier AU - Carol Astbury AU - Maria G. Belvisi AU - Carla A. Da Silva AU - Alexandra Jauhiainen AU - Eulalia Jimenez AU - Alejhandra Lei AU - Sofia Necander AU - Jaclyn A. Smith AU - Ulrika Wählby Hamrén AU - Wenjing Xin AU - Ioannis Psallidas Y1 - 2021/01/01 UR - http://erj.ersjournals.com/content/early/2021/08/12/13993003.00972-2021.abstract N2 - Background Navafenterol (AZD8871) belongs to a new class of bronchodilator, the single-molecule muscarinic antagonist and beta agonist (MABA), being developed for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the efficacy, pharmacokinetics and safety of navafenterol versus placebo and an active comparator treatment for moderate-to-severe COPD.Methods This phase 2a, randomised, multicentre (Germany and UK), double-blind, double-dummy, three-way complete crossover study (ClinicalTrials.gov identifier: NCT03645434) compared 2 weeks’ treatment of once-daily navafenterol 600 µg via inhalation with placebo and a fixed-dose combination bronchodilator (umeclidinium/vilanterol [UMEC/VI]; 62.5 µg/25 µg) in participants with moderate-to-severe COPD. The primary outcome was change from baseline in trough FEV1 on day 15. Secondary endpoints included: change from baseline in peak FEV1; change from baseline in breathlessness, cough and sputum scale (BCSS); change from baseline in COPD assessment tool (CAT); adverse events; and pharmacokinetics.Results Seventy-three participants were randomised. After 14 days, trough FEV1 was significantly improved with navafenterol compared with placebo (least-squares [LS] mean difference 0.202 L; p<0.0001). There was no significant difference in FEV1 between navafenterol and UMEC/VI (LS mean difference −0.046 L; p=0.075). COPD symptoms (CAT and BCSS) showed significantly greater improvements with both active treatments versus placebo (all p<0.005). Novel objective monitoring (VitaloJAK) showed that cough was reduced with both active treatments compared with placebo. Safety profiles were similar across the treatment groups and no serious adverse events were reported in the navafenterol treatment period.Conclusion Once-daily navafenterol was well tolerated, improved lung function and reduced COPD-related symptoms, similar to an established once-daily fixed-dose combination bronchodilator.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: D. Singh has received grants and personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Epiendo, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Mundipharma, Novartis, Pfizer, Pulmatrix, Sanofi, Teva, Theravance and Verona, and personal fees from Cipla, Genentech and Peptinnovate.Conflict of interest: J. Beier has received consultation fees from AstraZeneca, Berlin Chemie/Menarini, Chiesi and Pohl-Boskamp, and participated in scientific advisory boards that were funded by AstraZeneca and Chiesi.Conflict of interest: C. Astbury is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: M.G. Belvisi is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: C.A. Da Silva is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: A. Jauhiainen is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: E. Jimenez is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: A. Lei is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: S. Necander is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: MFT receives royalties which may be shared with the clinical division in which J.A. Smith works, and J.A. Smith has received personal fees from AstraZeneca.Conflict of interest: U. Wählby Hamrén is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: W. Xin is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd).Conflict of interest: I. Psallidas is employee of AstraZeneca and may hold stock or stock options. The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). ER -