Abstract
Introduction: GSK573719 is a new LAMA offering sustained 24-hour bronchodilation in development for the treatment of COPD.
Objectives: To investigate the safety, tolerability, PK and PD of GSK573719 in ipratropium-responsive COPD patients.
Methods: In a randomised, double-blind, dose-ascending, 4-way crossover study, 24 patients enrolled received single doses of 4 of the following 5 treatments by dry powder inhalation: GSK573719 (250/500/1000μg), placebo (PBO), tiotropium bromide (TB; 18μg). Doses were separated by 14 days.
Results: 20 patients completed all dosing periods. Adverse events (AEs) were reported with 31–41% GSK573719, 38% TB and 29% of PBO doses, most of mild or moderate intensity. There were 5 severe AEs and 4 patients withdrew due to AEs (none were drug related). No clinically meaningful differences in clinical chemistry, vital signs or ECG parameters were seen for GSK573719 vs PBO, although lower heart rates were observed for all active treatments (up to 7.7bpm lower with 1000μg vs PBO). GSK573719 was rapidly absorbed (median tmax 5–15min), but 40–61% of plasma PK samples were nonquantifiable. Urine t1/2 was on average 11–12h. Specific airway conductance (sGaw) and FEV1 responses were significantly higher for all active treatments vs PBO, and responses for all GSK573719 doses were higher than TB. No correlation was observed between GSK573719 systemic exposure and PD variables.
Conclusion: Single doses of GSK573719 250–1000μg were well tolerated and associated with clinically relevant improvements in lung function in COPD patients.
Funded by GSK (AC4108123; NCT00515502)
- © 2011 ERS