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 μg and racemic formoterol 12 and 24 μg (containing 6 and 12 μg (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 μg in 2 mL) and racemic formoterol (12 μg and 24 μg) 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 μg arformoterol and 12 μg 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 μg arformoterol resulted in 53% and 42% lower Cmax and AUC(0-tau) versus 24 μg 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 μg nebulized arformoterol was similar to 12 μg racemic formoterol DPI, and lower than 24 μg racemic formoterol DPI. Airway function improvement was similar for all groups.
CLINICAL IMPLICATIONS: Nebulized arformoterol 15 μg and racemic formoterol 12 μg via DPI resulted in similar plasma (R,R)-formoterol concentrations, and less than those of the 24-μg 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.