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Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator
BACKGROUND: Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β(2−)agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients w...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487995/ https://www.ncbi.nlm.nih.gov/pubmed/32907566 http://dx.doi.org/10.1186/s12931-020-01347-7 |
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author | Singh, Dave Balaguer, Victor Astbury, Carol Wählby-Hamrén, Ulrika Jimenez, Eulalia Seoane, Beatriz Villarroel, Cristina Lei, Alejhandra Aggarwal, Ajay Psallidas, Ioannis |
author_facet | Singh, Dave Balaguer, Victor Astbury, Carol Wählby-Hamrén, Ulrika Jimenez, Eulalia Seoane, Beatriz Villarroel, Cristina Lei, Alejhandra Aggarwal, Ajay Psallidas, Ioannis |
author_sort | Singh, Dave |
collection | PubMed |
description | BACKGROUND: Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β(2−)agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD. METHODS: This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 μg, navafenterol 1800 μg and placebo (all double-blind) and indacaterol 150 μg and tiotropium 18 μg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV(1)) on day 2. Safety and tolerability were monitored throughout. RESULTS: Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 μg and 1800 μg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV(1) (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P < .0001). The changes were significantly greater with navafenterol 1800 μg vs the active comparators (least squares mean treatment difference: 0.065–0.069 L, both P < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4–37.5%), slightly higher for navafenterol 400 μg (52.9%), and lowest for navafenterol 1800 μg (22.6%). CONCLUSIONS: Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02573155; URL: www.clinicaltrials.gov. Registered 9th October, 2015. |
format | Online Article Text |
id | pubmed-7487995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-74879952020-09-16 Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator Singh, Dave Balaguer, Victor Astbury, Carol Wählby-Hamrén, Ulrika Jimenez, Eulalia Seoane, Beatriz Villarroel, Cristina Lei, Alejhandra Aggarwal, Ajay Psallidas, Ioannis Respir Res Research BACKGROUND: Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β(2−)agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD. METHODS: This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 μg, navafenterol 1800 μg and placebo (all double-blind) and indacaterol 150 μg and tiotropium 18 μg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV(1)) on day 2. Safety and tolerability were monitored throughout. RESULTS: Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 μg and 1800 μg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV(1) (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P < .0001). The changes were significantly greater with navafenterol 1800 μg vs the active comparators (least squares mean treatment difference: 0.065–0.069 L, both P < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4–37.5%), slightly higher for navafenterol 400 μg (52.9%), and lowest for navafenterol 1800 μg (22.6%). CONCLUSIONS: Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02573155; URL: www.clinicaltrials.gov. Registered 9th October, 2015. BioMed Central 2020-09-09 2020 /pmc/articles/PMC7487995/ /pubmed/32907566 http://dx.doi.org/10.1186/s12931-020-01347-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Singh, Dave Balaguer, Victor Astbury, Carol Wählby-Hamrén, Ulrika Jimenez, Eulalia Seoane, Beatriz Villarroel, Cristina Lei, Alejhandra Aggarwal, Ajay Psallidas, Ioannis Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
title | Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
title_full | Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
title_fullStr | Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
title_full_unstemmed | Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
title_short | Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
title_sort | navafenterol (azd8871) in patients with copd: a randomized, double-blind, phase i study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487995/ https://www.ncbi.nlm.nih.gov/pubmed/32907566 http://dx.doi.org/10.1186/s12931-020-01347-7 |
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