title: Effects of mometasone furoate/formoterol fumarate fixed-dose combination formulation on chronic obstructive pulmonary disease (COPD): results from a 52-week Phase III trial in subjects with moderate-to-very severe COPD.
abstract: BACKGROUND
  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 (FEV(1)) over 0-12 hours (AUC(0-12 h) FEV(1)) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV(1) 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 AUC(0-12 h) FEV(1) 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 FEV(1), for which effects were further investigated, excluding subjects whose AM FEV(1) data were incorrectly collected after 2 days from the last dose of study treatment. Improvements in SGRQ scores surpassed the minimum clinically important difference of more than four units with both MF/F treatments. At 26 weeks, no notable between-treatment differences in the occurrence and nature of adverse events (AEs) were reported. No unexpected AEs were observed. Overall, 90 subjects reported AEs considered to be treatment-related, the most common of which were lenticular opacities, dysphonia, and oral candidiasis.
  
  
  CONCLUSIONS
  In conclusion, MF/F treatments improved lung function and respiratory health status, reduced exacerbations, and were well tolerated in subjects with moderate-to-very severe COPD.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY 40536, USA. dedohe0@email.uky.edu
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Doherty
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Knorr
authors.forename: Tulin
authors.initials: T
authors.lastname: Shekar
authors.forename: Sibabrata
authors.initials: S
authors.lastname: Banerjee
authors.forename: Heribert
authors.initials: H
authors.lastname: Staudinger
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013147:Spirometry; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D000068759:Formoterol Fumarate