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

• Published in: International journal of chronic obstructive pulmonary disease Vol. 7; no. default; pp. 43 - 55
• Main Authors: Tashkin, Donald P, Doherty, Dennis E, Kerwin, Edward, Matiz-Bueno, Carlos E, Knorr, Barbara, Shekar, Tulin, Banerjee, Sibabrata, Staudinger, Heribert
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2012; Dove Medical Press
• Subjects: Administration, Inhalation; Adult; Area Under Curve; Bronchodilator Agents - administration & dosage; Complications and side effects; Dosage and administration; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug therapy; Drug therapy, Combination; Ethanolamines - administration & dosage; Female; Formoterol; Formoterol Fumarate; Humans; Lung diseases, Obstructive; Male; Metered Dose Inhalers; Middle Aged; Mometasone; Mometasone Furoate; Original Research; Pregnadienediols - administration & dosage; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - pathology; Respiratory Function Tests; Severity of Illness Index; Smoking; Spirometry; Surveys and Questionnaires; Treatment Outcome; United States; FEV1; spirometry; inhaled corticosteroid; bronchodilator; chronic obstructive pulmonary disease; exacerbation
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S27319

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.
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 (FEV(1)) over 0-12 hours (AUC(0-12) FEV(1)) with MF/F versus MF, and in morning predose FEV(1) 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.
Significant improvements in FEV(1) AUC(0-12) 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 FEV(1) improvements with MF/F over the treatment period. Significant improvements in morning predose FEV(1) occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV(1) data were collected >2 days after the last dose of study treatment. Improvements in SGRQ total scores surpassed the minimum clinically important difference of at least 4 units with MF/F 400/10. MF/F 400/10 significantly reduced the time-to-first COPD exacerbation. Similar proportions of subjects in all five treatment groups reported treatment-emergent adverse events. Rates of pneumonia were low (≤1.0%) across treatment groups.
MF/F 400/10 μg twice daily was shown to be an effective therapy for patients with moderate to very severe COPD, and both MF/F 400/10 μg twice daily and MF/F 200/10 μg twice daily were well tolerated.