Sepracor Inc, Marlborough, Mass, presented clinical data for XOPENEX HFA® (levalbuterol tartrate) inhalation aerosol at the American College of Allergy, Asthma and Immunology annual meeting in Philadelphia. The study compared safety and tolerability of cumulative doses of XOPENEX HFA (hydrofluoroalkane) MDI (metered-dose inhaler) with those from a racemic albuterol HFA MDI in a group of patients with asthma.
The results demonstrated that both ( R )-albuterol systemic exposure and consequent beta-mediated adverse events were less following cumulative dosing with XOPENEX HFA when compared to cumulative dosing with racemic albuterol HFA MDI. Racemic albuterol HFA MDI contains both ( R )- and ( S )-albuterol, while XOPENEX HFA contains only ( R )-albuterol.
This study was designed to look at safety parameters associated with overdosing. Patients received excessive doses under medical supervision to evaluate these effects. The safety and efficacy results of this study do not support a comparison of the two products when used at recommended doses.
After completing screening and single-blind placebo run-in periods, asthmatic patients who met randomization criteria were administered either 16 cumulative puffs of XOPENEX HFA (45 mcg) (n=22) or racemic albuterol HFA MDI (90 mcg) (n=27) during the first dosing visit (Visit 4). Following a seven-day washout period, they were crossed-over and received a total of 16 puffs of the other treatment. Measures of heart rate, blood pressure, serum potassium and glucose concentrations were obtained pre-dose, after each dose, and up to eight hours after the final dose.
Changes in mean heart rate following one and two cumulative puffs did not differ significantly between the XOPENEX HFA and racemic albuterol HFA groups. However, changes in mean heart rate after 4, 8, and 16 cumulative puffs were significantly higher for racemic albuterol compared to XOPENEX HFA. Median ( R )-albuterol concentrations appeared to increase proportionally with dose for both treatments. Median plasma concentrations of ( R )-albuterol following each dose of racemic albuterol HFA were approximately 10% to 28% higher than those observed following the corresponding doses of XOPENEX HFA, and this difference in ( R )-albuterol levels became more pronounced with increased doses. When subjects received racemic albuterol HFA, median ( S )-albuterol concentrations were consistently two- to five-times higher than ( R )-albuterol concentrations.
Improvement in FEV1, which is a test of lung function that measures the amount of air forcefully exhaled in one second, was comparable between treatment groups, as were changes in serum potassium, glucose concentrations, and blood pressure.