Methods: MF/F’s effect on nocturnal awakenings requiring SABA was characterized across 3 phase III efficacy trials (baseline = number of nights with awakenings in week before first dose; endpoint = number of nights/wk with awakenings averaged across the 26-week treatment period). Subjects were asthmatics previously treated with low- (n=746), medium- (n=781) or high-dose (n=728) inhaled corticosteroids at various doses. Subjects in the MF/F 100/10μg BID study were randomized to 26 weeks of twice-daily (BID) treatment with MF/F 100/10μg, MF 100μg, F 10μg, or placebo; subjects in the MF/F 200/10μg BID study to 26 weeks of BID treatment with MF/F 200/10μg, MF 200μg, F 10μg, or placebo; and subjects in the MF/F 400/10μg BID study to 12 weeks of BID treatment with MF/F 400/10μg, MF/F 200/10μg, or MF 400μg. All treatments were delivered via a metered dose inhaler.
Results: Baseline awakenings ranged from 0.84–1.05, 1.05–1.26, and 1.33–1.61 nights/wk in the MF/F 100/10μg BID, MF/F 200/10μg BID, and MF/F 400/10μg BID studies, respectively. In the MF/F 100/10μg BID study, nocturnal awakenings were reduced by MF/F= –0.42, MF= –0.21, F= –0.21, and placebo= 0.14 nights/wk; corresponding changes in the MF/F 200/10μg BID study were –0.56, –0.35, +0.07 and 0.00 nights/wk, respectively. In each of these placebo-controlled studies, MF/F was superior to placebo (P<.001) and F (P≤.035); MF was also superior to F and placebo. In the MF/F 400/10μg BID study, awakenings were reduced by –0.70, –0.70 and –0.35 nights/wk by MF/F 200/10 μg, MF/F 400/10μg, and MF 400μg, respectively; both MF/F treatments were superior to MF (P≤.006).
Conclusions: These results provide evidence that validates the role of MF/F in reducing nocturnal asthma symptoms in patients with moderate to severe persistent asthma and supports the efficacy of MF/F compared with that of placebo and F.