ORLANDO – A combination of fixed-dose mometasone furoate and formoterol fumarate improved lung function in patients with moderate to very severe chronic obstructive pulmonary disease.
The finding came from a 26-week, phase III, multicenter, double-blind, placebo-controlled study of 1,055 adults who were current or former smokers and had a prebronchodilator forced expiratory volume in 1 second (FEV1)/ forced vital capacity ratio of 0.70 or less. Currently, three combinations of inhaled corticosteroid plus long-acting beta agonists are available for the treatment of COPD, but not this particular combination of mometasone furoate with formoterol fumarate administered with a metered-dose inhaler, which is licensed for asthma treatment in the United States under the name Dulera, Dr. Edward Kerwin said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The patients were randomized to one of five twice-daily metered-dose inhaler treatment arms: mometasone furoate 400 mcg/formoterol 10 mcg (MF400/F10), mometasone furoate 200 mcg/formoterol 10 mcg (MF200/F10), mometasone furoate 400 mcg alone (MF400), formoterol 10 mcg alone (F10), or placebo. A total of 840 of the 1,055 randomized patients completed the treatment period. About 80% of the patients were male, with a mean age of 59 years, and about three-quarters were white. Nearly half were current smokers, and all had smoked at one point in time, with an average of 40 pack-years.
The findings of this study also were published online in the International Journal of Chronic Obstructive Pulmonary Disease (Int. J. Chron. Obstruct. Pulmon. Dis. 2012;7:43-55).
One of the two coprimary endpoints, the contribution of F10 to the MF400/F10 combination at week 13, was reached with a statistically significant 109 mL difference in FEV1 area under the curve, compared with MF 400 alone. The overall effect size was a 163 mL difference for MF400/F10 over placebo at 13 weeks. A comparison of MF 400/F10 with MF 400 monotherapy also demonstrated a statistically significant effect of the F10, with an improvement of 69 mL, reported Dr. Kerwin, of the Clinical Research Institute of Southern Oregon, Medford.
The other coprimary endpoint, the mean change from baseline in morning predose FEV1 at the week 13 endpoint, showed the contribution of the MF component. It was statistically significant for MF400/F10 over F10 alone, at 111 mL, and for MF200/F10 over F10 alone, at 58 mL. An overall effect size of 128 mL was seen for MF400/F10 over placebo.
Among the secondary efficacy variables, the MF 400/F10 group exceeded the 4-point minimum clinically important difference on the St. George’s Respiratory Questionnaire, compared with placebo, with a significant effect size of 4.56 points at week 26. Statistically significant improvements in questionnaire total score for MF400/F10 over placebo were demonstrated at weeks 4, 13, and 26. However, the MF200/F10 dosage did not achieve the minimum clinically important difference, with only a 2.82 reduction, compared with placebo.
The proportion of COPD symptom–free nights improved by 0.15 with MF400/F10, compared with 0.06 for placebo, a significant difference over the 26-week period. However, there was no treatment difference between MF400/F10 and placebo in the proportion of patients with partly stable COPD at 26 weeks, with percentages ranging from 38% to 46% across treatment groups.
Time to first COPD exacerbation significantly improved with MF400/F10 over F10 alone, and an analysis excluding mild exacerbations showed that moderate to severe exacerbations were significantly more frequent with placebo than with MF400/F10, at 16.5% vs. 8.8%, Dr. Kerwin said.
Treatment with MF400/F10 was well tolerated, and the proportion of patients reporting treatment-emergent adverse events during the 26-week treatment period was similar between treatment groups, ranging from 26% in the MF400/F10 group to 33% in the F10 alone group. The most common of these were headache, upper respiratory tract infection, cough, COPD, and hypertension. Pneumonia did not occur in more than 1% in any treatment group. The incidence of oral candidiasis was low, occurring in no more than 2.4% of any group (five of the MF 400 alone patients), he reported.
This study was sponsored by Merck Sharp & Dohme. Dr. Kerwin disclosed that he has received consulting fees and/or speaking fees from Dey Laboratories, GlaxoSmithKline, MAP Pharma (AstraZeneca), Merck, Teva, and Sepracor.