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

Autor: Ulrika Wählby-Hamrén, Cristina Villarroel, Victor Balaguer, Alejhandra Lei, Beatriz Seoane, Dave Singh, Ajay Aggarwal, Eulalia Jimenez, Carol Astbury, Ioannis Psallidas
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Vital Capacity
Pulmonary Disease
Chronic Obstructive
0302 clinical medicine
Bronchodilator
Forced Expiratory Volume
Lung
COPD
Cross-Over Studies
MABA
Middle Aged
Bronchodilator Agents
Treatment Outcome
Tolerability
England
Anesthesia
Quinolines
Female
Safety
medicine.drug
medicine.drug_class
Bronchoconstriction
Muscarinic Antagonists
Placebo
03 medical and health sciences
Double-Blind Method
Dual-pharmacology muscarinic receptor antagonist β2-adrenoceptor agonist
Administration
Inhalation
medicine
Humans
Pharmacokinetics
Adverse effect
Adrenergic beta-2 Receptor Agonists
Aged
lcsh:RC705-779
business.industry
Research
lcsh:Diseases of the respiratory system
Recovery of Function
Triazoles
medicine.disease
Confidence interval
030104 developmental biology
030228 respiratory system
Pharmacodynamics
Indacaterol
business
Zdroj: Respiratory Research
Respiratory Research, Vol 21, Iss S1, Pp 1-11 (2020)
ISSN: 1465-993X
Popis: Background Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β2−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 (FEV1) 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 FEV1 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P P 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.
Databáze: OpenAIRE
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