PURPOSE: Airway function improvement with arformoterol, a long-acting β2 agonist that is the (R,R)-isomer of formoterol, and salmeterol were compared with placebo in patients with COPD in a multicenter, double-blind, double-dummy, randomized trial.
METHODS: Patients (mean age: 63 yrs, 60% male) had non-asthmatic COPD (mean FEV1 1.24 L, 41% predicted). Treated patients (n=739) received either nebulized arformoterol (15 μg BID, 25 μg BID, or 50 μg QD), salmeterol 42 μg BID (via MDI), or placebo BID for 12 weeks. The primary efficacy endpoint was the % change from baseline in morning trough FEV1 (12 hrs after the evening dose for the BID groups, 24 hours postdose for the QD group) modeled over 12 weeks.
RESULTS: The LSmean % improvement in morning trough FEV1 was greater in all arformoterol groups (15 μg BID: 15.7%; 25 μg BID: 21.0%, 50 μg QD: 17.8%) and in the salmeterol group (17.3%) than placebo (5.3%; p-values <0.001). After 12 weeks of daily dosing, all active treatments continued to provide significant improvement vs placebo (active: 12.9-16.2%; placebo: 4.6%; p-values ≤0.003). Improvements in the key secondary efficacy endpoint, the LSmean 0-12-hr % change in FEV1 AUC from predose (%Δ FEV1 AUC(0-12hr)) modeled over 12 weeks, were greater for arformoterol (13.5-19.4%) and salmeterol (10.7%) than for placebo (2.5%; p-values <0.001). At the end of 12 weeks, LSmean %Δ FEV1 AUC(0-12hr) values increased 9.2-15.5% for the arformoterol groups vs 2.2% for placebo (p-values <0.001); improvement for salmeterol was 5.8% (p=0.02 vs placebo). For this endpoint, significantly greater improvement was observed for all arformoterol doses vs salmeterol over the double-blind period and at 12 weeks (p-values ≤0.029). All treatments were well tolerated.
CONCLUSION: In this Phase 3 trial, arformoterol-treated patients demonstrated significant and sustained improvement in airway function over 12 weeks of treatment.
CLINICAL IMPLICATIONS: Nebulized arformoterol resulted in stable maintenance improvement of bronchoconstriction, and may be a beneficial therapy for patients with COPD. Support for this study provided by Sepracor Inc.
DISCLOSURE: J. Hanrahan, Employee Drs. Hanrahan, Sciarappa, McVicar, and Baumgartner are employees of Sepracor Inc.; Consultant fee, speaker bureau, advisory committee, etc. Dr. Smith is an investigator for Sepracor Inc.; Other Support for this study provided by Sepracor Inc.