The efficacy and safety of the novel long-acting β₂ agonist vilanterol in patients with COPD: A randomized placebo-controlled trial

Background: Vilanterol (GW642444M) (VI) is a novel, inhaled, long-acting β₂ agonist with inherent 24-h activity under development as a once-daily combination therapy with an inhaled corticosteroid for COPD and asthma. This study assessed the dose response, efficacy, and safety of VI at doses of 3 to 50 μg in patients with moderate to severe COPD. Methods: Six hundred two patients (intent-to-treat) were randomized (double-blind) to VI 3, 6.25, 12.5, 25, or 50 μg or placebo once daily for 28 days. The primary end point was change from baseline in trough FEV₁ at the end of the 28-day treatment period. Secondary end points included 0- to 24-h weighted mean FEV 1 on days 1 and 28 and time to increases of ≥ 100 mL or ≥ 12% from baseline FEV₁ on day 1. Safety assessments included adverse events, vital signs, ECG assessment, and clinical laboratory tests. Results: VI once daily for 28 days significantly improved trough FEV₁ in a dose-dependent manner vs placebo. Clinically relevant treatment differences of ≥ 130 mL in trough and 0- to 24-h weighted mean FEV₁ were observed with VI 25- and 50- μg doses vs placebo. All doses of VI were associated with a low incidence of treatment-related adverse events/serious adverse events, with no suggestion of effects on BP, pulse rate, QT intervals corrected for heart rate calculated by Fridericia formula, or blood glucose and potassium levels. Conclusions: VI 25 and 50 μg once daily provided both statistically and clinically relevant 24-h improvements in lung function in patients with COPD compared with placebo. All doses of VI had a safety and tolerability profile similar to placebo. Trial registry: ClinicalTrials.gov; No.: NCT00606684; URL: www.clinicaltrials.gov.