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Dennis E Doherty1, Donald P Tashkin2, Edward Kerwin3, Barbara A Knorr4, Tulin Shekar4, Sibabrata Banerjee4, Heribert Staudinger41Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3Clinical Research Institute of Southern Oregon, Medford, OR, 4Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USARationale: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The trial’s co-primary endpoints were mean changes from baseline, as area under the curve (AUC), in forced expiratory volume (FEV1) over 0–12 hours (AUC0-12 h FEV1) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV1 with MF/F versus F after 13 weeks of treatment. Key secondary endpoints were the effects of MF/F on respiratory health status using the Saint George’s Respiratory Questionnaire (SGRQ), symptom-free nights, partly stable COPD at 26 weeks, and time to first COPD exacerbation.Results: The largest improvements in AUC0-12 h FEV1 were observed with MF/F 400/10 µg and MF/F 200/10 µg. Serial spirometry results demonstrated that bronchodilator effects with MF/F occurred rapidly (within 5 minutes), persisted for 12 hours after dosing, and were sustained over the 26-week treatment period. Similar findings were observed for AM pre-dose FEV1, for which effects were further investigated

Tashkin DP, Doherty DE, Kerwin E, Matiz-Bueno CE, Knorr B, Shekar T, Banerjee S, Staudinger H. Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial. Int J Chron Obstruct Pulmon Dis. 2012;7:43–55.In Table 4, the value at column 5, row 15 should have been 4 instead of 2. Read the original article

Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Davis Gates5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR, USA; 4Fundación Salud Bosque, Bogota, Colombia, 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USABackground: The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).Methods: Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged ≥40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% of subjects on active treatment entered a 26-week safety extension. Coprimary efficacy variables were mean changes in forced expiratory volume in one second (FEV1), area under the curve from 0 to 12 hours postdose (AUC0–12 h), and morning predose/trough FEV1 from baseline to the week 13 endpoint. Key secondary efficacy variables were St George’s Respiratory Questionnaire scores, symptom-free nights, time-to-first exacerbation, and partly stable COPD at the week 26 endpoint.Results: In the 26-week treatment period, significantly greater increases in FEV1 AUC0–12 h occurred with MF/F 400/10 versus MF 400 and placebo at the week 13 and week 26 endpoints (P ≤ 0.032). These increases were over three-fold greater with MF/F 4

Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Sibabrata Banerjee5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR USA; 4Fundación Salud Bosque, Bogota, Colombia; 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ USABackground: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1) over 0–12 hours (AUC0–12 FEV1) with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ]), symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.Results: Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007). Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding r