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 beta(2) 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 mu g 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 mu g 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 FEV1 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-mu g 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 mu g 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 CHEST 2012; 142(1):119-127