188 Efficacy Comparison of Mometasone Furoate/Formoterol Versus Fluticasone Propionate/Salmeterol Combination Therapies in Subjects With Persistent Asthma: Noninferiority and Onset-of-Action Findings

BACKGROUND: Mometasone furoate/formoterol (MF/F) combination therapy is a new treatment recently approved by the US Food and Drug Administration for the treatment of persistent asthma and currently under regulatory review by Canadian authorities. We report findings from a noninferiority study that compared effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma. METHODS: This randomized, active-controlled, multicenter, noninferiority trial enrolled subjects (aged ≥12 years) previously treated with medium-dose inhaled corticosteroid alone or combined with a long-acting β(2)-agonist. Following a 2- to 4-week run-in treatment period with MF administered via a metered-dose inhaler (MDI) 200 μg twice daily (BID), eligible subjects were randomized to MF/F-MDI 200/10 μg BID or FP/S administered via a dry powder inhaler (DPI) 250/50 μg BID for 12 weeks. The primary endpoint of this trial was change from baseline in area under the curve (AUC) in forced expiratory volume in 1 second (FEV(1)) measured serially for 0 to 12 hours postdose (FEV(1) AUC(0−12h)). Key secondary endpoints included onset of action, defined as change from baseline in FEV(1) at 5 minutes postdose on day 1. RESULTS: 722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). The trial's primary endpoint was met, demonstrating that MF/F administered via an MDI was noninferior to FP/S administered via a DPI in the patient population investigated. Mean FEV(1) AUC(0−12h) at endpoint for MF/F-MDI and FP/S-DPI was 3.43 versus 3.24 L × h, respectively (95%, CI, −0.40 to 0.76). Analysis of onset-of-action characteristics revealed that MF/F's effect on lung function occurred significantly faster than the effect observed with FP/S-DPI. MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV(1) at 5 minutes postdose (first scheduled measurement) on the first day of treatment vs a 90-mL increase for FP/S-DPI (P < 0.001). CONCLUSIONS: This trial demonstrated that MF/F 200/10 μg BID administered via an MDI was noninferior to FP/S 250/50 μg BID administered via a DPI in its effect to improve lung function as measured by FEV1 AUC0–12h. However, the onset of action for this effect was significantly faster with MF/F-MDI than with FP/S-DPI.