PURPOSE: To investigate whether the combination of mometasone furoate/formoterol (MF/F) administered via a metered-dose inhaler can improve lung function in subjects with chronic obstructive pulmonary disease (COPD). MF/F has been shown to improve lung function and reduce clinical deteriorations in asthma patients ≥12y. We report findings from 2 trials characterizing the effect of MF/F in subjects with moderate−very severe COPD.
METHODS: Two 26-wk, multicenter, double-blind, placebo (PBO)-controlled trials included current/ex-smokers (≥10 pack-y) with moderate−very severe COPD (mean baseline [BL] % predicted FEV1, 39.6% [Trial 1]; 38.7% [Trial 2]). Subjects (≥40y) were randomized to twice-daily (BID) inhaled MF/F 400/10µg (n1=217; n2=225, respectively), MF/F 200/10µg (n1=207; n2=239), MF 400µg (n1=210; n2=253), F 10µg (n1=209; n2=243), or PBO (n1=212; n2=236). Efficacy was characterized by measuring mean changes from BL in FEV1 over 0−12 hrs (AUC0−12 FEV1) and pre-dose AM FEV1 after 13 wks of treatment.
RESULTS: The largest improvements in AUC0−12 FEV1 from BL were observed with MF/F 400/10µg and MF/F 200/10µg; for MF/F 400/10µg, MF/F 200/10µg, MF 400µg, F 10µg, PBO, respectively, the improvements were 166,* 126,* 57, 77, 3 mL (Trial 1); and 179,* 139,* 53, 92, 18 mL (Trial 2; *P≤0.007 vs MF 400µg in each trial). Similar findings were observed in pre-dose AM FEV1 change from BL (111,† 58,† 27, 0, -17 mL [Trial 1]; and 98, 63, 28, 49, -3 mL [Trial 2]; for MF/F 400/10µg, MF/F 200/10µg, MF 400µg, F 10µg, PBO; †P≤0.029 vs F). Pre-dose AM FEV1 was further investigated, excluding subjects whose AM FEV1 data were incorrectly collected >24 hrs (n1=30; n2=32) after the last dose of study treatment (112,‡ 53, 24, 2, -29 mL [Trial 1] and 98,‡ 61, 27, 40, -7 mL [Trial 2] for MF/F 400/10µg, MF/F 200/10µg, MF 400µg, F 10µg, PBO, respectively; ‡P≤0.030 vs F). At 26 wks, no notable between-treatment differences in the occurrence/nature of adverse events (AEs) were reported. Incidences of treatment-related AEs were: 6.0%, 4.3%, 5.7%, 7.2%, 4.7% (Trial 1); and 8.4%, 5.4%, 9.9%, 7.8%, 5.9% (Trial 2; for MF/F 400/10µg, MF/F 200/10µg, MF 400µg, F 10µg, PBO, respectively, in each trial). No unexpected AEs were observed; MF/F was considered well tolerated.
CONCLUSIONS: MF/F 400/10µg and 200/10µg BID significantly improved lung function and were well tolerated in subjects with moderate−very severe COPD.
CLINICAL IMPLICATIONS: Inhalation of MF/F 400/10µg BID and MF/F 200/10µg BID improved lung function in subjects with moderate−very severe COPD.
DISCLOSURE: Dennis Doherty: University grant monies: Boehringer Ingelheim, Merck, Novartis, Pfizer, Grant monies (from sources other than industry): NIH-NHLBI, Department of Veterans Affairs, Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Boehringer Ingelheim, Forest, Ikaria, Merck, Pfizer
Donald Tashkin: University grant monies: Merck, Consultant fee, speaker bureau, advisory committee, etc.: Merck
Edward Kerwin: Grant monies (from industry related sources): Merck
Carlos Eduardo Matiz-Bueno: Other: Spouse is an employee at Merck
Tulin Shekar: Employee: Merck
Sibabrata Banerjee: Employee: Merck
Jonathan Sadeh: Employee: Merck
No Product/Research Disclosure Information