title: Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials.
abstract: BACKGROUND
  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 (FEV(1)), area under the curve from 0 to 12 hours postdose (AUC(0-12 h)), and morning predose/trough FEV(1) 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 FEV(1) AUC(0-12 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 400/10 than with MF 400. Also, significantly greater increases in morning predose/trough FEV(1) occurred with MF/F 400/10 versus F 10 and placebo at the week 13 endpoint (P < 0.05). The increase was four-fold greater with MF/F 400/10 than with F 10. All active treatment groups achieved minimum clinically important differences from baseline (>4 units) in St George's Respiratory Questionnaire scores at week 26. Symptom-free nights increased by ≥14% in the MF/F 400/10, MF 400, and F 10 groups (P ≤ 0.033 versus placebo). The incidence of exacerbations was lower in the MF/F groups (≤33.3%) than it was in the MF, formoterol, and placebo groups (≥33.8%) over the 26-week treatment period. The incidence of adverse events was similar in the active-treated and placebo-treated subjects across 26 weeks of treatment. Over the 1-year study period, there were no notable differences in the incidence or types of adverse events between the MF/F 400/10 and MF/F 200/10 groups compared with the MF or formoterol groups. Differences in rates of individual treatment-emergent adverse events were <3% between treatment groups. Rates of pneumonia were low (≤2%) across all treatment groups.
  
  
  CONCLUSIONS
  Patients treated with MF/F demonstrated significant improvements in lung function, health status, and exacerbation rates. Although significant improvements were seen with both doses, a trend showing a dose-response effect was observed in the lung function measurements.
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: Davis
authors.initials: D
authors.lastname: Gates
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; 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; 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