title: 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.
abstract: BACKGROUND
  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 (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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. dtashkin@mednet.ucla.edu
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Doherty
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Matiz-Bueno
authors.forename: Barbara
authors.initials: B
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; D012907:Smoking; D013147:Spirometry; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D000068759:Formoterol Fumarate