Navafenterol (AZD8871) in healthy volunteers: safety, tolerability and pharmacokinetics of multiple ascending doses of t
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RESEARCH
Open Access
Navafenterol (AZD8871) in healthy volunteers: safety, tolerability and pharmacokinetics of multiple ascending doses of this novel inhaled, long-acting, dual-pharmacology bronchodilator, in two phase I, randomised, single-blind, placebocontrolled studies Victor Balaguer1, Muna Albayaty2, Eulalia Jimenez3, Ulrika Wählby-Hamrén4, Carol Astbury1, Beatriz Seoane5, Marie-Pierre Malice6, Alejhandra Lei7, Ajay Aggarwal8 and Ioannis Psallidas9*
Abstract Background: Navafenterol (AZD8871) is a novel, long-acting, dual-pharmacology (muscarinic receptor antagonist and β2−adrenoceptor agonist) molecule in development for chronic obstructive pulmonary disease and asthma. Methods: These two phase I, randomised, single-blind, multiple-ascending-dose studies evaluated inhaled navafenterol and placebo (3:1 ratio) in healthy, male, non-Japanese (study A; NCT02814656) and Japanese (study B; NCT03159442) volunteers. In each study, volunteers were dosed in three cohorts, allowing gradual dose escalation from 300 μg to 600 μg to 900 μg. The primary objective was to investigate the safety and tolerability of navafenterol at steady state. Pharmacokinetics were also assessed. Results: Twenty-four volunteers completed each study (navafenterol, n = 6; placebo, n = 2 in each cohort). There were no deaths, serious adverse events (AEs) or treatment-emergent AEs (TEAEs) leading to discontinuation of navafenterol. The most frequent TEAEs were vessel puncture-site bruise (placebo, n = 2; navafenterol 900 μg; n = 3) in study A and diarrhoea (placebo, n = 1; navafenterol 300 μg, n = 2; navafenterol 900 μg, n = 3) in study B. No doseresponse relationship was observed for TEAEs. There was a dose-dependent increase in mean heart rate on day 16 in both studies. The pharmacokinetics of navafenterol were similar between non-Japanese and Japanese volunteers. (Continued on next page)
* Correspondence: [email protected] 9 Research and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This 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 wai
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