AUGMENT Study Results Show Combination Therapy Superior to Monotherapy for COPD

May 20, 2014
Julian Kaye, PhD

Treatment with a fixed-dose combination of aclidinium 400 µg and formoterol 12 µg significantly improved bronchodilation in patients with moderate to severe COPD compared with aclidinium or formoterol monotherapy alone.

Bronchodilators are central to the management of chronic obstructive pulmonary disease (COPD). Two or more bronchodilators with different mechanisms of action are recommended for more effective management of COPD. A fixed-dose combination, administered via a single inhaler, provides a more convenient option than using separate devices.

During a poster discussion session at the 2014 American Thoracic Society International Conference, Anthony D’Urzo, MD, Associate Professor in the Department of Family and Community Medicine at the University of Toronto and director of the Primary Care Lung Clinic, suggested that combining bronchodilators from different therapeutic classes may increase treatment efficacy while decreasing the frequency of adverse events.

D’Urzo presented data on lung function improvements from the phase 3 24-week, double-blind, parallel-group AUGMENT COPD trial of the fixed-dose combination of aclidinium, a long-acting muscarinic antagonist (LAMA) indicated for maintenance treatment of COPD-associated bronchospasm, and formoterol, a long-acting β2-agonist (LABA), in patients with moderate to severe COPD.

In the study, patients were randomized 1:1:1:1:1 to receive twice-daily inhaled aclidinium/formoterol combination (400 µg/12 µg), aclidinium/formoterol combination (400 µg/6 µg), aclidinium 400 µg monotherapy, formoterol 12 µg monotherapy, or placebo.

The coprimary outcomes were the change in forced expiratory volume in one second (FEV1) value (measured each morning one hour after patients received medication) at Week 24 compared to the corresponding measurement at baseline, and the change in morning pre-dose trough FEV1 at Week 24 compared with baseline (Day 1). The combination agent was evaluated against aclidinium alone to assess the contribution of formoterol and against formoterol alone to assess the contribution of aclidinium.

The researchers also measured changes from baseline in one-hour morning post-dose, trough, and peak FEV1 during several visits during the study.

The study included 1,668 patients with a mean baseline pre-bronchodilator FEV1 of 1.36 L and a mean predicted post-bronchodilator FEV1 of 53.5%.

Researchers reported that morning one-hour post-dose FEV1 was significantly improved in patients who received either fixed-dose combination of aclidinium/formoterol compared to patients who received aclidinium alone.

Patients who received treatment with aclidinium/formoterol 400 µg/12 µg showed significant improvements in trough FEV1 at week 24 compared to patients who received formoterol monotherapy, an effect that was not seen with the other fixed combination dose.

Treatment with both fixed-dose combinations of aclidinium/formoterol was associated with significant improvement in trough FEV1 compared with placebo.

Treatment with either fixed-dose combination of aclidinium/formoterol produced greater improvements in peak FEV1 compared with aclidinium or formoterol monotherapy, or placebo.

The aclidinium/formoterol 400 µg/12 µg combination was consistently associated with greater improvements in lung function measurements compared with aclidinium/formoterol 400 µg/6 µg.

Based on these results, the researchers concluded that treatment with a fixed-dose combination of aclidinium 400 µg and formoterol 12 µg significantly improved bronchodilation compared with aclidinium or formoterol monotherapy and placebo (usually p<0.0001). Furthermore, the improvements were maintained throughout the 24-week study period.