Efficacy and safety of mometasone furoate administered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids

Background: Once-daily dosing with an inhaled corticosteroid (ICS) may simplify asthma management and improve patient compliance. Since asthma is frequently worse at night, evening dosing appears to be a more obvious choice to accommodate the chronobiology of asthma than morning dosing. Objective: The primary study objective was to compare the efficacy and safety of mometasone furoate (MF) dry powder inhaler (MF-DPI) 400 mu g qd PM (one 400 mu g inhalation) with placebo for the treatment of asthma in patients previously dependent on twice a day (bid, bis in die) ICS therapy. We also compared different regimens of MF-DPI with each other and with placebo. Methods: This 12-week, multicenter, double-blind, placebo-controlled study evaluated lung function and asthma symptoms in 400 subjects with persistent asthma randomized to MF-DPI 200 mu g qd (once a day, quaque die) PM, 400 mu g qd PM as one inhalation from a 400 mu g device, 400 mu g qd PM as two inhalations from a 200 mu g device, 200 mu g twice daily (bid), or placebo. Evening doses were to be taken in the late afternoon or early evening, preferably before dinner time. Results: Mean changes from baseline at endpoint in FEV1 (forced expiratory volume in 1 s) were similar for MF-DPI 400 mu g qd PM (one inhalation; 0.41 L), MF-DPI 400 mu g qd PM (2 inhalations; 0.49 L), MF-DPI 200 mu g qd PM (0.41 L), and MF-DPI 200 mu g bid (0.51 L); and all were significantly improved compared with placebo (0.16 L; p < 0.001). Secondary efficacy variables, including nocturnal awakenings and use of rescue albuterol, were also significantly improved with MF-DPI treatment compared with placebo. All treatments were generally safe and well tolerated, with adverse events of mild to moderate severity. Conclusions: Once-daily evening dosing of MF-DPI at doses of 400 and 200 mu g restored lung function and improved nocturnal and daytime symptom control in subjects with asthma previously dependent on bid ICS therapy. Comparable effectiveness of a total daily dose of 400 mu g was demonstrated between once daily in the evening and twice-daily administration. The results also confirm the effectiveness of MF-DPI 200 mu g qd PM, the lowest dose studied.