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

Int J Chron Obstruct Pulmon Dis. 2012;7:57-71. doi: 10.2147/COPD.S27320. Epub 2012 Feb 3.


Rationale: 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.

Discussion: 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.

Trial registration: ClinicalTrials.gov NCT00383721.

Keywords: COPD; FEV1; bronchodilator; exacerbation; inhaled corticosteroid; spirometry.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Area Under Curve
  • Bronchodilator Agents / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Ethanolamines / administration & dosage*
  • Female
  • Formoterol Fumarate
  • Humans
  • Male
  • Metered Dose Inhalers
  • Middle Aged
  • Mometasone Furoate
  • Pregnadienediols / administration & dosage*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Respiratory Function Tests
  • Severity of Illness Index
  • Spirometry
  • Treatment Outcome


  • Bronchodilator Agents
  • Drug Combinations
  • Ethanolamines
  • Pregnadienediols
  • Mometasone Furoate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT00383721