RT Journal Article
SR Electronic
T1 Phase II study of once-daily GSK573719 inhalation powder, a new long-acting muscarinic antagonist, in patients with chronic obstructive pulmonary disease (COPD)
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p834
VO 38
IS Suppl 55
A1 Dennis Kelleher
A1 Andrew Preece
A1 Rashmi Mehta
A1 Alison Donald
A1 Kelly Hardes
A1 Anthony Cahn
A1 Glenn Crater
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p834.abstract
AB 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)