This study evaluated the dose-response and dosing interval of the novel long-acting muscarinic receptor antagonist (LAMA) GSK573719 in patients with COPD.

This randomized, double-blind, placebo-controlled, 3-way cross-over, incomplete block study evaluated 5 once-daily doses of GSK573719 (62.5–1000 μg), 3 twice-daily doses (62.5–250 μg), and open-label tiotropium for 14 days in patients (N = 176) with COPD (FEV₁ of 35–70% predicted). The primary endpoint was morning trough FEV₁ at Day 15. Secondary endpoints included 0–24 h weighted mean FEV₁ and serial FEV₁ values over 28 h. Safety measures and pharmacokinetics were assessed.

All once-daily doses of GSK573719 significantly increased trough FEV₁ at Day 15 with improvements ranging from 95 to 186 mL over placebo (p ≤ 0.006), from 79 to 172 mL with twice-daily dosing (p ≤ 0.03), and 105 mL with tiotropium (p = 0.003). No clear dose ordering was observed. Once-daily doses significantly (p < 0.001) increased 0–24 h weighted mean FEV₁ at Day 14 by 131–143 mL over placebo, comparable to increases with the twice-daily doses (120–142 mL) and tiotropium (127 mL). Significant reductions in rescue albuterol use and improvements in FVC were also observed with once-daily dosing. Plasma C_max occurred within 5–15 min of dosing after which the drug was rapidly cleared and eliminated. GSK573719 was well tolerated, with no apparent treatment-related changes in vital signs, ECG and Holter assessments, or clinical laboratory parameters.

Once-daily dosing with GSK573719 in COPD provides clinically significant and sustained improvement in lung function over 24 h with similar efficacy to twice-daily dosing.