Chest
Volume 142, Issue 1, July 2012, Pages 119-127
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Original Research
COPD
The Efficacy and Safety of the Novel Long-Acting β2 Agonist Vilanterol in Patients With COPD: A Randomized Placebo-Controlled Trial

https://doi.org/10.1378/chest.11-2231Get rights and content

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 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-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.

Section snippets

Study Population

Men and women aged 40 to 80 years with a history of COPD and ≥ 10 pack-years of smoking were enrolled. At screening, eligible patients had a measured post-albuterol/salbutamol FEV1/FVC ratio of ≤ 0.70 and an FEV1 of ≥ 35% and ≤ 70% of predicted.

Medications not permitted during the study are detailed in e-Table 1. Reasons for exclusion included current diagnosis of asthma, α1-antitrypsin deficiency, and receipt of long-term oxygen therapy. Complete inclusion/exclusion criteria are detailed in

Study Population

A total of 605 patients were randomized; the ITT population comprised 602 patients, and 539 (90%) completed the study (Fig 1). The primary reasons for withdrawing early from the study were protocol deviation (n = 20), AE (n = 12), investigator discretion (n = 12), or reaching protocol-defined withdrawal criteria (n = 10).

Baseline demographic and clinical characteristics were similar across treatment groups (Table 1). The majority of patients in each treatment group were male, white, and graded

Discussion

Our study demonstrates that the novel long-acting β2 agonist VI is effective and well tolerated in patients with COPD. Treatment with VI once daily at doses ranging from 3 μg to 50 μg for 28 days produced statistically significant, dose-dependent improvements in trough FEV1 (primary outcome measure) compared with placebo. An improvement from baseline FEV1 of ≥ 100 mL represents a clinically relevant treatment difference.11 Adjusted mean treatment differences of ≥ 100 mL vs placebo in both

Acknowledgments

Author contributions: All authors vouch for the accuracy and completeness of the data and the data analysis.

Dr Hanania: contributed as a study principal investigator, had full access to and interpreted the data, and wrote the manuscript.

Dr Feldman: contributed as a study principal investigator, had full access to and interpreted the data, and wrote the manuscript.

Dr Zachgo: contributed as a study principal investigator, had full access to and interpreted the data, and wrote the manuscript.

Dr

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This study was funded by GlaxoSmithKline.

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