189 Efficacy and Safety of Two Doses of Mometasone Furoate/Formoterol Combination Treatment in Subjects With Severe Asthma

BACKGROUND: Multiple strengths of mometasone furoate/formoterol (MF/F) metered-dose inhaler combination therapy have been investigated as new treatments for asthma. We report efficacy/safety findings from an MF/F study in subjects with severe asthma previously uncontrolled on high-dose inhaled corticosteroids (ICS) with or without a long-acting ß(2)-agonist (LABA). METHODS: This was a 3-month, randomized, double-blind, parallel-group, multicenter study with a 2- to 3-week open-label run-in period during which subjects received mometasone furoate (MF) 400 μg twice daily (BID). Subjects (≥12 years) were randomized to MF/F 200/10 μg BID, MF/F 400/10 μg BID, or MF 400 μg BID. The primary endpoint was the area under the curve (AUC) of the change in serial (0−12 hours) forced expiratory volume in 1 second (FEV(1)) for MF/F 400/10 μg vs MF 400 μg from baseline to week 12. Adverse events (AEs) and other clinical safety measures were recorded. RESULTS: 728 subjects were randomized (mean: age, 47.9 years; asthma duration, 14.0 years; FEV(1) % predicted, 66.3; reversibility, 22.9%; Asthma Control Questionnaire score, 1.93). Improvements in mean changes from baseline in FEV(1) AUC(0−12h) at week 12 were: MF/F 200/10 μg = 3.59 L × h; MF/F 400/10 μg = 4.19 L × h; MF 400 μg = 2.04 L × h, with both MF/F doses significantly better than MF (P < 0.001). These FEV(1) AUC(0–12h) values with MF/F 200/10 μg, MF/F 400/10 μg, and MF 400 μg correspond to average hourly increases of 0.30, 0.35, and 0.17 L, respectively. MF/F was associated with a rapid (<5 minutes) and sustained improvement in lung function. The percentages of subjects experiencing an asthma deterioration (ie, severe asthma exacerbation) were 12.4% (MF/F 200/10 μg), 12.2% (MF/F 400/10 μg), and 18.3% (MF 400 μg). There were no notable differences in AEs between the groups. CONCLUSIONS: Both the 200/10 μg BID and 400/10 μg BID doses of MF/F combination therapy led to significantly greater improvements in lung function compared with 400 μg BID MF monotherapy in subjects with severe asthma previously treated with an ICS alone or in combination with LABA.