SESSION TYPE: COPD Posters II
PRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 01:30 PM
PURPOSE: Data from two dose-ranging studies of the inhaled long-acting muscarinic antagonist umeclidinium bromide (UMEC, GSK573719) were combined to assess the dose-response and dosing interval in patients with COPD (FEV1 ≥35 and ≤70% predicted).
METHODS: Data from two multicentre, randomized, double-blind, placebo-controlled studies, were analyzed (NCT00950807; NCT01372410) evaluating doses ranging from 15.6 to 1000 mcg once daily and 15.6 to 250 mcg twice daily. Tiotropium was included as an open-label active control. Primary endpoint was trough FEV1 at the end of the designated treatment period; a population model-based analysis was applied with ANCOVA supportive analysis. Secondary endpoints included serial FEV1 over 24 hours.
RESULTS: Data from 321 patients (mean age 59.9 years, 52% female) were examined. Modeling demonstrated a monotonic dose response over once and twice daily dosing. The ED50 was 33 mcg (range 29-41) and Emax 187 mL (range 165-209). No difference in once daily and twice daily dosing regimens was identified (pooled data). UMEC doses ≥62.5 mcg once daily can be differentiated from lower doses. All UMEC doses significantly increased trough FEV1 at the end of treatment compared with placebo, improvements ranged from 97 mL (p=0.002) to 189 mL (p<0.001) with once-daily dosing, and from 83 mL (p=0.012) to 173 mL (p<0.001) with twice-daily dosing. A 106 mL (p<0.001) increase was observed for tiotropium. All once-daily doses of UMEC significantly (p<0.001) increased 0-24 hour weighted mean FEV1 at the end of treatment by 105 to 152 mL compared with placebo and were similar to increases observed with twice-daily dosing (123-145 mL).
CONCLUSIONS: Umeclidinium doses ≥62.5 mcg once daily were differentiated from lower UMEC once daily doses and a once-daily dosing regimen was confirmed. Funded and conducted by GlaxoSmithKline (Protocol AC4116689)
CLINICAL IMPLICATIONS: N/A
DISCLOSURE: Alison Church: Employee: GlaxoSmithKline
Christopher Kalberg: Employee: GlaxoSmithKline
Palvi Shah: Employee: GlaxoSmithKline
Misba Beerahee: Employee: GlaxoSmithKline
James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceuticals, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer and Sunovion, Grant monies (from industry related sources): Has received research grants from Boehringer Ingelheim, GlaxoSmithKline and Novartis
N/AResearch & Development; GlaxoSmithKline, Research Triangle Park, NC