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

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.

• Authors: Dennis E Doherty, Donald P Tashkin, Edward Kerwin, Barbara A Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 7 Pg. 57-71 ( 2012) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 22334769 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Respiratory Function Tests
• Severity of Illness Index
• Spirometry
• Treatment Outcome