Abstract
Introduction: GSK573719 is a new long-acting muscarinic antagonist offering sustained 24-hour bronchodilation in development for the treatment of COPD.
Objectives: To evaluate the safety, tolerability and pharmacokinetics of inhaled GSK573719 in a new dry powder (DP) formulation in COPD patients.
Methods: In this randomised, double-blind study, 38 patients with COPD received GSK573719 (250μg, n=20; 1000μg, n=9) or placebo (n=9) via a novel DP inhaler (DPI) once daily for 7 days.
Results: Of 43 adverse events (AEs) in 21 (55%) patients, 16 were drug related (all mild or moderate): placebo, 4 (headache, pruritus, flushing, hypoaesthesia); GSK573719 250μg, 5 (arrhythmia, tachycardia, dysgeusia, hypertension, bronchospasm); GSK573719 1000μg, 7 (blood pressure increase, thirst, oropharyngeal pain, headache, dry mouth, dyspnoea, feeling abnormal). Of 3 AE-related withdrawals (chest pain, respiratory tract infection, dyspnoea), only dyspnoea was considered drug-related (1000μg). The 1000μg dose showed larger increases than 250μg in heart rate (HR) (0–4h) vs placebo, but 24-h Holter monitoring showed no dose effect over 24h and the treatment effects were small. GSK573719 was rapidly absorbed (tmax 5–15min); 1–2% of the total dose was excreted unchanged in the urine. Accumulation (Day 7:Day 1) was low: 1.5–1.9x based on plasma data (1.8–2.4x, urine data). No correlation was seen between individual maximum HR (0–4h) and GSK573719 Cmax.
Conclusions: GSK573719 250μg or 1000μg once daily by novel DPI was well tolerated by patients with COPD.
Funded by GSK (AC4105211; NCT00732472)
- © 2011 ERS