GOLD guidelines recommend short-acting β2-agonists (SABAs) for symptom control across all severities of chronic obstructive pulmonary disease (COPD) and state that exacerbations affect quality of life and decrease health status. This study assessed the efficacy and safety of levalbuterol in treatment of patients with COPD.
This double-blind, placebo-controlled study evaluated patients with COPD who were ≥35 years of age, had FEV1 ≤65% predicted and >0.70 L, a ≥15 pack-year smoking history, and a medical research council dyspnea scale score of ≥2. Stable doses of inhaled corticosteroids were allowed. Patients were randomized to nebulized levalbuterol 1.25mg (n=49), levalbuterol 0.63mg (n=53), racemic albuterol (RAC) 2.5mg (n=52), or placebo (n=55) TID for 6 weeks. Patients returned to clinic every 2 weeks for serial spirometry and assessment of dyspnea and rescue medication use (MDI SABA and ipratropium). COPD symptoms and exacerbations, adverse events (AEs), and dropouts were monitored throughout. At the 4-week visit only, response to study drug added to ipratropium bromide was assessed.
Mean time-normalized AUC percent change FEV1 (AUC %Δ FEV1) was significantly greater (p<0.001) following all active treatments relative to placebo. Concomitant administration of levalbuterol 1.25mg with ipratropium resulted in significantly greater (p=0.009) AUC %Δ FEV1 than ipratropium with placebo. Rescue medication use increased in the RAC and placebo groups, was unchanged in the levalbuterol 0.63mg group, and significantly decreased in the levalbuterol 1.25mg group (p=0.02 vs RAC). RAC-treated patients had the most COPD exacerbations and significantly more study withdrawals due to COPD exacerbations when compared with placebo (p=0.01). AE rates and beta-mediated side effects were lowest in the levalbuterol 0.63mg group, although all active treatments were well tolerated.
In this study, levalbuterol was well tolerated, produced significant bronchodilation, and reduced rescue medication use. RAC was associated with significantly more study withdrawals due to COPD exacerbations compared with placebo.
Levalbuterol may offer advantages in the treatment of patients with COPD.
James Donohue, Consultant fee, speaker bureau, advisory committee, etc. I am a paid consultant for Sepracor and serve on their Advisory Board. I have also participated as an investigator in several clinical trials for Sepracor, including the one presented here.