Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator

Background: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. Objectives: To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 mug twice a day; Glare Wellcome, Research Triangle Park, NC) was used as an active control. Design: A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. Setting: Sixty centers in 20 countries. Patients: Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. I nterventions: Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 mug twice daily) and one of FP (250 mug twice daily >12 weeks). Results: FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 mug twice daily of MF-DPI (+0.19 L) was statistically different from 100 mug twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 mug twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 mug twice daily of MF-DPI or with FP Diskhaler, compared with 100 mug twice daily of MF-DPI, Overall, a total daily 800-mug dose of MF-DPI conferred no significant additional benefit >400 mug of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 mug twice daily of MF-DPI and FP groups, respectively. Conclusions: A total daily dose of 400 mug of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 mug of FP Diskhaler.