Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma

Abstract

Background: Mometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the 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: Following a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 μg (delivered as 2 inhalations of MF-MDI 100 μg) twice daily (BID), subjects (aged ≥12 y) were randomized to MF/F-MDI 200/10 μg BID (delivered as 2 inhalations of MF/F-MDI 100/5 μg) or FP/S administered via a dry powder inhaler (DPI) 250/50 μg (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV1 AUC0-12 h). Secondary assessments included onset of action (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient-reported outcomes.

Results: 722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). Mean FEV1 AUC0-12 h change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L × h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]).

Conclusions: The results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints.

Trial registration: ClinicalTrials.gov: NCT00424008.

Figure 1

Study Design*. BID = twice daily; DPI = dry powder inhaler; FP/S = fluticasone propionate/salmeterol; MDI = metered-dose inhaler; MF = mometasone furoate; MF/F = mometasone furoate/formoterol. *Doses were delivered via 2 actuations of an MDI (MF 100 μg or MF/F 100/5 μg) or 1 actuation of a DPI (FP/S 250/50 μg) BID. ^†In the MF/F-MDI 200/10 μg BID treatment group, 42% of subjects discontinued. ^‡In the FP/S-DPI 250/50 μg BID treatment group, 41% of subjects discontinued.

Figure 2

Serial FEV₁ (0-12 h) and Standardized FEV₁ AUC_{0-12 h} at Week 12 (LOCF). AUC = area under the curve; BID = twice daily; DPI = dry powder inhaler; FEV₁ = forced expiratory volume in 1 second; FP/S = fluticasone propionate/salmeterol; LOCF = last observation carried forward; MDI = metered-dose inhaler; MF/F = mometasone furoate/formoterol.

Figure 3

Onset of Action: Serial FEV₁ (0-1 h) at Day 1. BID = twice daily; DPI = dry powder inhaler; FEV₁ = forced expiratory volume in 1 second; FP/S = fluticasone propionate/salmeterol; MDI = metered-dose inhaler; MF/F = mometasone furoate/formoterol. *P < 0.001.

Figure 4

Mean Total ACQ* (top) and AQLQ(S)^† (bottom) Scores. ACQ = Asthma Control Questionnaire; AQLQ(S) = Asthma Quality of Life Questionnaire With Standardized. Activities; BID = twice daily; DPI = dry powder inhaler; FP/S = fluticasone propionate/salmeterol; LOCF = last observation carried forward; MDI = metered-dose inhaler; MF/F = mometasone furoate/formoterol; MID = minimally important difference. *ACQ score based on a 7-point scale that ranged from 0 (best asthma control) to 6 (worst asthma control). ^†AQLQ(S) score based on a 7-point scale that ranged from 1 (worst quality of life) to 7 (best quality of life).

Figure 5

Proportion of Symptom-Free Days and Nights. BID = twice daily; DPI = dry powder inhaler; FP/S = fluticasone propionate/salmeterol; LOCF = last observation carried forward; MDI = metered-dose inhaler; MF/F = mometasone furoate/formoterol.