PURPOSE: Examine the long-term safety of levalbuterol (LEV) HFA administered via metered dose inhaler (MDI) in patients with stable asthma.
METHODS: Mild-to-moderate asthmatics (mean FEV1 2.2L, 68.3% predicted) ≥12 years participated in a multicenter, parallel group, open-label study. After a 7-day QID single-blind placebo HFA MDI run-in, patients were randomized in a 2:1 ratio to equivalent doses of (R)-albuterol in LEV MDI (90 μg; 2 actuations of 45 μg (R)-albuterol; n=496) or racemic albuterol (RAC) MDI (180 μg; 2 actuations of 90 μg (R)-albuterol and 90 μg (S)-albuterol; n=250) for up to 52 weeks of QID dosing. The primary endpoint was the incidence of post-randomization adverse events (AEs). Asthma attacks, laboratory evaluations, electrocardiograms, and the % change in FEV1 from visit predose were also assessed.
RESULTS: The incidence of AEs was similar for LEV (72.0%) and RAC (76.8%). Rates of β2-mediated AEs were 18.8% and 25.6%, respectively. The incidence of serious AEs (3.6% and 5.2%, respectively) and discontinuations due to AEs (9.1% and 9.6%, respectively) were also similar. No deaths occurred. Rates of asthma AEs were 18.3% and 19.6%, respectively, and rates of asthma attacks were 16.3% and 18.4%. Small mean changes in potassium occurred in both groups (LEV: post-first dose −0.03 mEq/L, at 52 weeks −0.02 mEq/L; RAC: post-first dose −0.05 mEq/L; at 52 weeks −0.06 mEq/L). No statistically significant differences were noted at 52 weeks for changes in ventricular heart rate or QTc-F. Mean % changes in FEV1 one hour post-first dose were 18.1% and 16.3% for LEV and RAC, respectively; and 12.7% and 11.6% at week 52, respectively.
CONCLUSION: In this trial, LEV MDI administered as 90 μg QID for up to 52 weeks was generally well-tolerated.
CLINICAL IMPLICATIONS: Long-term treatment (up to one year) with LEV HFA MDI is well tolerated in patients with mild-to-moderate asthma, suggesting that it may be an appropriate treatment now available for use in the management of reversible airways obstruction. Support for this study provided by Sepracor Inc.
DISCLOSURE: M. Parsey, Employee Drs. Parsey, McVicar and Baumgartner, and Mr. Tripp, are employees of Sepracor Inc.; Consultant fee, speaker bureau, advisory committee, etc. Drs. Smith and Marcus are investigators for Sepracor Inc. Dr. Marcus has served on the Xopenex Speaker Bureau; Other Support for this study provided by Sepracor Inc.