PT - JOURNAL ARTICLE AU - Virginia Norris AU - Chang-Qing Zhu AU - Claire Ambery TI - The pharmacodynamics of GSK961081 in patients with COPD DP - 2011 Sep 01 TA - European Respiratory Journal PG - p823 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p823.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p823.full SO - Eur Respir J2011 Sep 01; 38 AB - Introduction: GSK961081 is a dual pharmacophore with both muscarinic antagonist and beta2 agonist (MABA) activity.Objective: To assess the pharmacodynamics of GSK961081.Methods: This was a randomised, double-blind, double-dummy, placebo-controlled, incomplete block crossover study in 50 COPD patients. Patients were randomised to 3 of 4 possible treatments: 400μg GSK961081 once daily (OD) (n=29); 1200μg GSK961081 OD (n=32); salmeterol 50μg twice daily+tiotropium 18μg OD (SAL+TIO) (n=41); and placebo (n=43) by inhalation for 14 days. Pharmacodynamics (lung and systemic), safety and tolerability were monitored.Results: After 14 days' dosing there were significant improvements in trough FEV1 for all active treatments. For 400μg GSK961081, 1200μg GSK961081 and SAL+TIO mean (95% CI) differences vs placebo were 0.115L (0.024,0.205), 0.168L (0.080,0.255) and 0.103L (0.026,0.180), respectively (all p<0.05). There was no significant difference in maximum change from baseline heart rate, glucose or QTcF 0–4h after the final dose of any active treatment vs placebo. There was a small decrease in potassium 0–4h after the final dose of all active treatments. For 400μg GSK961081, 1200μg GSK961081 and SAL+TIO mean (95% CI) minimum change from baseline potassium vs placebo was –0.11 (–0.22,–0.01), –0.19 (–0.29,–0.09) and –0.10 (–0.19,–0.01) mmol/L, respectively. Adverse events were similar across all groups with the exception of tremor (n=2, 1200μg dose), dysguesia (n=2, 1200μg dose; n=2, 400μg dose) and dry mouth (n=1, 1200μg dose) seen after GSK961081 only.Conclusions: GSK961081 was well tolerated and showed significant bronchodilatation, meriting further evaluation as a potential therapy for COPD.Funded by GSK (MAB104958; NCT00478738)