@article {Cahnp3971, author = {Anthony Cahn and Rosalind Lovick and Amy Newlands and Amanda Deans and Isabelle Pouliquen and Andrew Preece and Dennis Kelleher and Rashmi Mehta and Ruth Tal-Singer}, title = {Safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of GSK573719 inhalation powder in healthy subjects}, volume = {38}, number = {Suppl 55}, elocation-id = {p3971}, year = {2011}, publisher = {European Respiratory Society}, abstract = {Introduction: GSK573719 is a new long-acting muscarinic antagonist offering sustained 24-hour bronchodilation in development for the treatment of chronic obstructive pulmonary disease (COPD).Objectives: To investigate the safety, tolerability, PD and PK of single inhaled doses of GSK573719.Methods: This double-blind, placebo-controlled, crossover, dose-escalation study randomised 20 ipratropium-responsive healthy male subjects to GSK573719 (10{\textendash}350μg), tiotropium bromide (TB; 18μg) and placebo.Results: Eighteen subjects completed all 5 treatment periods. Adverse events (AEs) were mainly mild-to-moderate; no serious AEs were reported. One severe non-drug related AE was reported (increased creatine phosphokinase). 95\% confidence intervals were assessed for statistical significance of PD data. Significantly higher specific airways conductance (sGaw) was observed, versus placebo, for GSK573719 100 and 250μg at 12h, and for GSK573719 350μg and TB at 12h and 24h. FEV1 values were also significantly greater than placebo for GSK573719 100 and 350μg at 12h and 24h and for TB at 24h. GSK573719 plasma Cmax (maximum plasma concentration) occurred at a median tmax of 5min, followed by a rapid decline to below the lower limit of quantification by 6h. Between subjects Cmax variability was moderate-to-high (38{\textendash}57\%).Conclusion: In this first-in-human study, GSK573719 demonstrated adequate safety, tolerability and prolonged bronchodilation, suggesting the potential for once-daily administration in COPD.Funded by GSK (AC4105209)}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/38/Suppl_55/p3971}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }