Long-term Efficacy and Safety of Fluticasone Propionate Powder Administered Once or Twice Daily via Inhaler to Patients With Moderate Asthma

Abstract

To evaluate the efficacy and safety of fluticasone propionate administered as a once-daily or twice-daily regimen over a period of 1 year to patients with moderate asthma. Double-blind, randomized, parallel group, and placebo-controlled phase (12 weeks) and an open-label phase (54 weeks). Multicenter study in an outpatient setting. Patients (n = 253; age, > or = 12 years) with a mean FEV(1) of 67% predicted normal were stratified according to baseline therapy of maintenance inhaled corticosteroids vs beta(2)-agonists alone. Fluticasone propionate (250 microg bid or 500 microg qd) or placebo (bid) was administered via the Diskus multidose powder inhaler (Glaxo Wellcome; Research Triangle Park, NC) for 12 weeks. During open-label treatment, patients were re-randomized to once-daily or twice-daily fluticasone propionate. Compared to placebo, fluticasone propionate administered qd or bid significantly improved FEV(1) (p < 0.001), morning (p < 0.001) and evening peak expiratory flow (PEF; p < 0.001), asthma symptom scores (p < or = 0.001), and albuterol use (p </= 0.001), and decreased nighttime awakenings. By the end of 12 weeks, withdrawal due to lack of efficacy was significantly higher in the placebo group than in the once-daily (p = 0.001) or twice-daily (p < 0.001) groups. When comparing the two active dosing regimens, significant differences in favor of twice-daily dosing were noted in FEV(1), albuterol use, and withdrawal due to lack of efficacy. During 54 weeks of open-label treatment, FEV(1) and PEF continued to improve with both regimens, and improvements seen in the first 12 weeks were maintained in patients who switched from twice-daily to once-daily dosing. Fluticasone propionate treatment over a 54-week period was well tolerated, with few drug-related adverse events, which were primarily topical effects of inhaled corticosteroids. Fluticasone propionate powder improved lung function when administered either qd or bid over a 1-year period to patients with moderate asthma, with twice-daily dosing demonstrating significantly greater improvement in some efficacy parameters than once-daily dosing over the first 12 weeks of treatment. Fluticasone propionate treatment was not associated with significant systemic effects.