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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, placebo-controlled studies.
- Source :
- Respiratory Research; 9/9/2020, Vol. 21 Issue 1, p1-12, 12p
- Publication Year :
- 2020
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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 dose-response 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.<bold>Conclusions: </bold>Multiple ascending doses of navafenterol were well-tolerated and the safety and pharmacokinetics of navafenterol were similar in non-Japanese and Japanese volunteers. The findings support navafenterol clinical development.<bold>Trial Registration: </bold>ClinicalTrials.gov ; Nos.: NCT02814656 and NCT03159442; URL: www.clinicaltrials.gov . [ABSTRACT FROM AUTHOR]
- Subjects :
- PHARMACOKINETICS
VOLUNTEERS
OBSTRUCTIVE lung diseases
MUSCARINIC receptors
MUSCARINIC antagonists
ADRENERGIC beta agonists
QUINOLINE
RESEARCH
HUMAN research subjects
CLINICAL trials
HETEROCYCLIC compounds
RESEARCH methodology
MEDICAL cooperation
EVALUATION research
BRONCHODILATOR agents
COMPARATIVE studies
BLIND experiment
INHALATION administration
Subjects
Details
- Language :
- English
- ISSN :
- 14659921
- Volume :
- 21
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Respiratory Research
- Publication Type :
- Academic Journal
- Accession number :
- 145653344
- Full Text :
- https://doi.org/10.1186/s12931-020-01474-1