AN OPEN LABEL STUDY OF ARFORMOTEROL INHALATION SOLUTION AND RACEMIC FORMOTEROL DRY POWDER INHALER IN SUBJECTS WITH COPD

Abstract

PURPOSE: Arformoterol, the (R,R)-isomer of formoterol, is a nebulized long-acting beta2-agonist approved for the long-term maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD). This study compared exposure (plasma concentrations of (R,R)-formoterol) and forced expiratory volume in 1 second (FEV1) for nebulized arformoterol 15 {micro}g and racemic formoterol 12 and 24 {micro}g (containing 6 and 12 {micro}g (R,R)-formoterol, respectively) delivered by dry powder inhaler (DPI). METHODS: An open-label, randomized, 3-way crossover study in 39 subjects (FEV1 1.4L, 44.4% predicted) who received BID treatment with arformoterol (15 {micro}g in 2 mL) and racemic formoterol (12 {micro}g and 24 {micro}g) for 14 days. Plasma concentrations of (R,R)-formoterol were determined on the first, 12th, and 13th days of treatment. FEV1 was assessed at predose and over the 12-hour dosing period on the first and last days of treatment. RESULTS: After the first dose and at 14 days, plasma exposure to (R,R)-formoterol was similar following nebulized 15 {micro}g arformoterol and 12 {micro}g racemic formoterol. The steady state treatment ratios and 90% confidence intervals for Cmax and AUC(0-tau) were 0.91 (0.76, 1.09) and 1.16 (1.00, 1.35), respectively. Treatment with 15 {micro}g arformoterol resulted in 53% and 42% lower Cmax and AUC(0-tau) versus 24 {micro}g racemic formoterol. The mean percent increases in baseline trough FEV1 after 14 days were 19.1% in the arformoterol group, and 16.0% and 18.2% in the respective racemic formoterol groups. The tolerability profile was similar in all groups. CONCLUSION: In this study, post-first dose and steady state exposure to (R,R)-formoterol following treatment with 15 {micro}g nebulized arformoterol was similar to 12 {micro}g racemic formoterol DPI, and lower than 24 {micro}g racemic formoterol DPI. Airway function improvement was similar for all groups. CLINICAL IMPLICATIONS: Nebulized arformoterol 15 {micro}g and racemic formoterol 12 {micro}g via DPI resulted in similar plasma (R,R)-formoterol concentrations, and less than those of the 24-{micro}g racemic formoterol dose. There was similar bronchodilator efficacy and tolerability for all treatments. DISCLOSURE: Jahnavi Kharidia, No Product/Research Disclosure Information; Employee Full-time employee of Sepracor Inc.