A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD
Respiratory Medicine, 05/18/2012
Donohue JF et al. – 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.Methods
- 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 Cmax 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.