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

• Published in: Respiratory research 2020-09, Vol.21 (Suppl 1), p.102-11, Article 102
• Main Authors: Singh, Dave, Balaguer, Victor, Astbury, Carol, Wählby-Hamrén, Ulrika, Jimenez, Eulalia, Seoane, Beatriz, Villarroel, Cristina, Lei, Alejhandra, Aggarwal, Ajay, Psallidas, Ioannis
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; Adrenergic beta-2 Receptor Agonists - pharmacokinetics; Aged; Bronchoconstriction - drug effects; Bronchodilation; Bronchodilator; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; Bronchodilator Agents - pharmacokinetics; Bronchodilators; Chronic obstructive pulmonary disease; Comparators; Confidence intervals; COPD; Cross-Over Studies; Double-Blind Method; Double-blind studies; Drug dosages; Dual-pharmacology muscarinic receptor antagonist β2-adrenoceptor agonist; England; Female; Forced Expiratory Volume; Humans; Informed consent; Laboratories; Least squares; Lung - drug effects; Lung - physiopathology; Lung diseases; MABA; Male; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Muscarinic Antagonists - pharmacokinetics; Obstructive lung disease; Patients; Pharmacodynamics; Pharmacokinetics; Pharmacology; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Quinolines - administration & dosage; Quinolines - adverse effects; Quinolines - pharmacokinetics; Recovery of Function; Safety; Statistical analysis; Thoracic surgery; Treatment Outcome; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - pharmacokinetics; Vital Capacity
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-020-01347-7

Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β 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. 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 ) on day 2. Safety and tolerability were monitored throughout. 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 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P